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Jun 01 – Jun 08, 2026
A randomised study of encorafenib, cetuximab, and FOLFIRI versus FOLFIRI with or without bevacizumab in BRAF V600E-mutant colorectal cancer: BREAKWATER Cohort 3.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
The randomized phase of the BREAKWATER trial (Cohort 3) evaluated first-line encorafenib plus cetuximab with FOLFIRI versus FOLFIRI ± bevacizumab in 147 patients with previously untreated BRAF V600E-mutant metastatic colorectal cancer. Patients were assigned 1:1, and outcomes were assessed by blinded independent central review; primary endpoint was objective response rate (ORR), with progression-free survival (PFS), overall survival (OS), and safety as secondary endpoints. EC+FOLFIRI significantly improved ORR (64.4% vs 39.2%; OR 2.76, 95% CI 1.42-5.35; P = 0.0011) and PFS (median 15.2 vs 8.3 months; HR 0.44, 95% CI 0.27-0.70; P = 0.0002), and showed prolonged OS (HR 0.56, 95% CI 0.34-0.94; median not estimable vs 20.3 months). Serious adverse events occurred in 49.3% of EC+FOLFIRI and 44.1% of controls, with safety consistent with known profiles. Investigators conclude EC+FOLFIRI provides a new standard of care for this population.
10.1016/j.annonc.2026.04.017
Fovinaciclib for First-Line Therapy of Advanced Breast Cancer: A Randomized Clinical Trial.
JAMA ONCOL · Q1 JOURNAL - RANK #14/326TOP-TIER
This double-blind, phase 3 randomized clinical trial evaluated the efficacy and safety of fovinaciclib combined with aromatase inhibitors as first-line therapy for hormone receptor-positive, ERBB2-negative advanced breast cancer. Enrolled between March 2022 and June 2023, 417 adult women were randomized 1:1 to receive fovinaciclib or placebo with letrozole/anastrozole; premenopausal patients also received goserelin. At an interim analysis with a median follow-up of 16.6 months, fovinaciclib significantly improved median progression-free survival (not reached vs. 20.2 months; HR, 0.55; 95% CI, 0.38-0.77; 1-sided P < .001) with consistent benefits across subgroups, manageable hematologic adverse effects, and no significant quality-of-life differences. These findings suggest clinically meaningful benefits for using fovinaciclib in this population, though overall survival data remain immature.
10.1001/jamaoncol.2026.1938
Robust Findings for HER2 TKI in NSCLC.
CANCER DISCOV · Q1 JOURNAL - RANK #10/326TOP-TIER
This study evaluates the clinical efficacy of zongertinib, a HER2 tyrosine kinase inhibitor (TKI), in treating HER2-mutant non-small cell lung cancer (NSCLC). Among 74 patients who received a daily dose, the objective response rate was 76%, and the median progression-free survival was 14.4 months, significantly outperforming traditional chemotherapy response rates of approximately 30% and a median duration of under 7 months. The findings suggest that zongertinib offers a notable improvement compared to the standard treatment options. These results highlight the potential of targeted therapies in advancing the treatment landscape for HER2-mutant NSCLC patients.
10.1158/2159-8290.CD-NW2026-0051
PARP and Androgen-Signaling Inhibition plus ADT in Metastatic Prostate Cancer.
NEW ENGL J MED · Q1 JOURNAL - RANK #2/332TOP-TIER
This phase 3, double-blind trial evaluated the efficacy of talazoparib plus enzalutamide versus placebo plus enzalutamide in 599 patients with metastatic androgen pathway modulation-sensitive prostate cancer harboring homologous recombination repair gene alterations. Patients were randomized 1:1, stratified by disease status, volume, and mutation status, with primary and secondary endpoints of imaging-based progression-free survival (PFS) and overall survival (OS), respectively. At 3 years, PFS was 77% in the talazoparib group versus 56% in the control group (HR 0.48; 95% CI, 0.36-0.65; P<0.001), while OS was 78% versus 72% (HR 0.77; 95% CI, 0.56-1.04). The study concluded that talazoparib significantly improved PFS but was associated with higher rates of serious adverse events (42% vs. 32%), including grade 3+ anemia (51%).
10.1056/NEJMoa2604126
Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer.
NEW ENGL J MED · Q1 JOURNAL - RANK #2/332TOP-TIER
This phase 3, international, open-label randomized trial evaluated daraxonrasib versus chemotherapy in patients with previously treated metastatic pancreatic ductal adenocarcinoma (mPDAC). A total of 500 participants were randomized, with 91.8% harboring G12 mutations, to receive either daraxonrasib or chemotherapy. Daraxonrasib significantly improved median overall survival (13.2 months vs. 6.6 months in the G12 population, HR: 0.40, P<0.001) and progression-free survival (7.3 months vs. 3.5 months in the G12 population, HR: 0.45, P<0.001). Adverse events occurred in all patients in the daraxonrasib group and 97.7% of the chemotherapy group, with fewer treatment-related discontinuations in the daraxonrasib group (1.2%) compared to the chemotherapy group (11.2%).
10.1056/NEJMoa2605555
Perioperative Apalutamide in High-Risk Localized Prostate Cancer.
NEW ENGL J MED · Q1 JOURNAL - RANK #2/332TOP-TIER
This phase 3, double-blind, placebo-controlled trial evaluated perioperative apalutamide plus androgen-deprivation therapy (ADT) in 2109 patients with high-risk localized prostate cancer undergoing radical prostatectomy. Patients were randomized 1:1 to ADT plus apalutamide (240 mg/day) or ADT plus placebo for 6 cycles before and after surgery. Pathological complete response or minimal residual disease was significantly higher with apalutamide (8.9% vs. 1.0%; OR, 10.17; P<0.001), and 5-year metastasis-free survival was improved (78.2% vs. 73.5%; HR, 0.80; P=0.02). The authors conclude that perioperative ADT plus apalutamide improves oncologic outcomes over ADT plus placebo, albeit with more adverse events.
10.1056/NEJMoa2603878
EP4 Antagonist ONO-4578 Plus Nivolumab and Chemotherapy in HER2-Negative Unresectable Advanced or Recurrent Gastric or Gastroesophageal Junction Cancer.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This multicenter, double-blind, randomized phase 2 trial investigated whether adding the EP4 antagonist ONO-4578 to nivolumab plus oxaliplatin-based chemotherapy improves outcomes in chemotherapy-naïve patients with HER2-negative unresectable or recurrent gastric/gastroesophageal junction cancer. Two hundred twenty-six patients were randomized 2:1 to ONO-4578 (n = 150) or placebo (n = 76) combined with nivolumab and chemotherapy; the primary endpoint was investigator-assessed progression-free survival (PFS), with overall survival (OS), objective response rate (ORR) and safety as secondary endpoints. The ONO-4578 arm showed superior PFS (HR 0.67; 90% CI 0.48–0.92; p = 0.040), improved OS at interim analysis (HR 0.60; 95% CI 0.37–0.96) and higher ORR (62.0% vs 48.7%); diarrhea (55.7%) and anemia (55.0%) were common adverse events. The authors conclude that ONO-4578 plus nivolumab and chemotherapy offers promising first-line efficacy with acceptable safety, meriting phase 3 confirmation.
10.1200/JCO-26-01072
Intismeran Autogene Plus Pembrolizumab Versus Pembrolizumab Alone in High-Risk Resected Melanoma: 5-Year Update of the Randomized Phase 2b KEYNOTE-942 Study.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This randomized phase 2b KEYNOTE-942 study evaluated intismeran (mRNA neoantigen therapy) plus pembrolizumab versus pembrolizumab alone in 157 patients with resected stage IIIB-IV melanoma. Over 60.3 months median follow-up, the combination prolonged recurrence-free survival (HR 0.510; 95% CI 0.294-0.887) and distant metastasis-free survival (HR 0.411; 95% CI 0.200-0.843) with a favorable overall survival trend (HR 0.471; 95% CI 0.165-1.345). Safety was manageable with no new signals. The combination showed increased T-cell receptor clonality and greater novel clone expansion in recurrence-free patients.
10.1200/JCO-26-00835
Pemigatinib for Unresectable or Metastatic Cholangiocarcinoma With Fibroblast Growth Factor Receptor-2 Rearrangement: Results From the Phase 3 FIGHT-302 Trial.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This phase 3, randomized, global trial (FIGHT-302) evaluated pemigatinib as first-line therapy in adults with advanced FGFR2-rearranged cholangiocarcinoma. One hundred sixty-seven patients were randomized to pemigatinib (13.5 mg daily) or chemotherapy (gemcitabine/cisplatin), with crossover allowed. Median progression-free survival was 8.3 vs 6.8 months (HR 0.58; p=0.0078), objective response rate 47% vs 15%, and median overall survival 24.4 vs 25.0 months. Pemigatinib demonstrated superior PFS versus chemotherapy with consistent safety, supporting its use as first-line targeted therapy for this population.
10.1200/JCO-26-00788
Targeting Fibroblast Activation Protein with [177Lu]Lu-FAP-2286 in Patients with Advanced Solid Tumors in the Phase I LuMIERE Trial.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
The LuMIERE trial is a prospective, open-label, non-randomized phase I/II clinical study evaluating the safety and efficacy of radiopharmaceutical therapy [177Lu]Lu-FAP-2286 in heavily pretreated patients with advanced solid tumors. Phase I employed a Bayesian optimal interval design to assess dosage-limiting toxicities (DLTs) across four dosage levels (3.70–9.25 GBq), administered intravenously every six weeks for up to six cycles. Two DLTs were reported, with one Grade 4 lymphopenia and one Grade 3 hemoptysis at doses of 5.55 GBq and 9.25 GBq, respectively, and the recommended phase II dose (RP2D) was identified as 9.25 GBq. Efficacy data showed one partial response and stable disease in 10 patients, warranting further investigation in phase II studies.
10.1158/1078-0432.CCR-25-4356
Dynamic genetic and nongenetic RAS pathway activation drives resistance to FLT3 and BCL2 inhibitor therapy.
BLOOD · Q1 JOURNAL - RANK #2/98TOP-TIER
This Phase 1b trial of combined venetoclax (BCL2 inhibitor) and gilteritinib (FLT3 inhibitor) in patients with acute myeloid leukemia aimed to characterize mechanisms of resistance. They used multiomic single-cell DNA/protein and RNA/protein profiling to analyze malignant clones and transcriptional states. While venetoclax and gilteritinib therapy eliminated FLT3-mutant clones, diverse RAS-activating events emerged, including selection for RAS mutations, non-mutational upregulation of RAS pathways, and a phenotypic switch to monocytic AML. RAS pathway inhibition restored sensitivity to venetoclax/gilteritinib, suggesting a potent therapeutic strategy against acquired resistance.
10.1182/blood.2025032466
Adjuvant Nivolumab vs Observation in Resected Non-Small Cell Lung Cancer: A Randomized Clinical Trial.
JAMA-J AM MED ASSOC · Q1 JOURNAL - RANK #4/332TOP-TIER
This open-label, randomized phase 3 clinical trial evaluated adjuvant nivolumab versus observation in 935 patients with resected non-small cell lung cancer (NSCLC) following planned adjuvant therapy. Patients were randomized 1:1 to receive nivolumab 480 mg intravenously every 4 weeks for up to 1 year or standard observation, with co-primary endpoints of disease-free survival (DFS) in the intention-to-treat population and in those with PD-L1 ≥50%. After median 72.6 months follow-up, median DFS was 71.3 months with nivolumab vs 68.8 months with observation (HR 0.97; 95% CI 0.81-1.17; p=0.39), and in the PD-L1 ≥50% subset, 89.8 vs 78.5 months (HR 0.86; 95% CI 0.59-1.25; p=0.22). The authors concluded adjuvant nivolumab did not improve DFS in this patient population.
10.1001/jama.2026.8992
Aglatimagene besadenovec (CAN-2409) with radiotherapy for patients with localised prostate cancer: a phase 3, multicentre, randomised, double-blind, placebo-controlled trial.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This phase 3, randomised, double-blind, placebo-controlled trial evaluated whether aglatimagene besadenovec (CAN-2409) with valacyclovir and external beam radiation therapy (EBRT) improves disease-free survival in patients with localised prostate cancer. Conducted across 51 centers, 745 men aged ≥18 were randomized (2:1) to receive aglatimagene or placebo alongside EBRT and optional androgen deprivation therapy (ADT). After a median follow-up of 50.3 months, the aglatimagene group had a significantly longer median disease-free survival (not reached, 95% CI 121.78–NR) compared to placebo (86.1 months, IQR 29.7–143.0; HR 0.70; p=0.016) without substantially increased severe treatment-related adverse events. The study concluded that aglatimagene with valacyclovir offers clinically meaningful benefits in prolonging disease-free survival without a significant rise in serious toxicity for this patient population.
10.1016/S1470-2045(26)00071-9
Perioperative serplulimab with neoadjuvant chemotherapy versus perioperative chemotherapy in PD-L1-positive gastric cancer (ASTRUM-006): a randomised, double-blind, multicentre, phase 3 study.
LANCET · Q1 JOURNAL - RANK #1/332TOP-TIER
This randomized, double-blind, multicentre phase 3 trial (ASTRUM-006) evaluated perioperative serplulimab with neoadjuvant SOX chemotherapy versus perioperative SOX chemotherapy alone in 588 patients with PD-L1-positive, resectable gastric or gastro-oesophageal junction adenocarcinoma. Patients were randomly allocated to receive serplulimab or placebo with SOX for three cycles preoperatively, followed by adjuvant serplulimab or SOX. Median event-free survival was significantly prolonged with serplulimab (not reached vs 42.0 months; HR 0.65, 95% CI 0.47–0.90, p=0.0082 in CPS ≥10; not reached vs 35.9 months, HR 0.73, 95% CI 0.56–0.94, p=0.015 in ITT), with fewer grade 3 or worse adverse events. The authors concluded this regimen improves event-free survival and safety for this patient group.
10.1016/S0140-6736(26)00974-8
Chemotherapy for patients with circulating tumour DNA positive, stage II colon cancer (CIRCULATE) - an AIO / ABCSG trial.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This prospective multi-center trial aimed to evaluate the role of adjuvant chemotherapy for ctDNA-positive stage II colon cancer using an academic tumor-informed NGS-based test. Patients with ctDNA positivity were randomized 2:1 to receive chemotherapy (capecitabine ± oxaliplatin) or observation, while ctDNA-negative patients were also randomized to observation or off-study. Despite early study termination, the per-protocol results revealed improved time-to-recurrence and disease-free survival with chemotherapy in ctDNA-positive patients (3-year recurrence: 19% vs 62%, HR 0.23, P=0.009). Although the primary ITT endpoint was not met, these data support using ctDNA testing to guide adjuvant therapy decisions in stage II colon cancer.
10.1016/j.annonc.2026.05.001
Dual epitope anti-LILRB4 synthetic T-cell receptor and antigen receptor (STAR)-T-cell therapy for relapsed/refractory acute myeloid leukemia.
SIGNAL TRANSDUCT TAR · Q1 JOURNAL - RANK #1/319TOP-TIER
This first-in-human, prospective clinical trial (NCT05548088) evaluated dual-epitope nanobody-based anti-LILRB4 synthetic T-cell receptor and antigen receptor (STAR) T-cell therapy in nine adults with relapsed/refractory LILRB4-positive acute myeloid leukemia. Patients received a single infusion of autologous STAR-T cells and were followed for a median of 10.7 months; six patients were evaluable for safety and efficacy. No grade ≥3 cytokine release syndrome or ICANS occurred, although three patients died from documented infections. The best overall response rate was 50 % (3/6) in the efficacy set and 33.3 % in the full cohort, with on-treatment expansion of LILRB4-targeted STAR-T cells and reduction of LILRB4-positive blasts; single-cell RNA-seq suggested monocyte-mediated T-cell suppression in nonresponders.
10.1038/s41392-026-02765-7
Sintilimab plus concurrent chemoradiotherapy for treatment of locally advanced small cell lung cancer (SINCE-01): a phase II clinical trial.
SIGNAL TRANSDUCT TAR · Q1 JOURNAL - RANK #1/319TOP-TIER
This single-arm phase II trial evaluated sintilimab combined with concurrent chemoradiotherapy (CCRT) in 22 patients with histologically confirmed limited-stage small cell lung cancer and good performance status. Patients received four 3-weekly chemotherapy cycles plus sintilimab with thoracic radiation (45 Gy in 30 fractions); the primary endpoint was progression-free survival (PFS). After 44.7 months median follow-up, median PFS was 29.6 months (12- and 24-month PFS 72.7% and 54.5%), median overall survival 40.6 months (12- and 24-month OS 95.5% and 72.7%), and objective response rate 95.5%; grade 3–4 toxicities were mainly hematologic, pneumonitis occurred in 3 patients (≥G2 in one), and no treatment-related deaths occurred. Higher tumor HLA-I expression correlated with longer PFS, supporting concurrent sintilimab-CCRT as effective with manageable safety.
10.1038/s41392-026-02668-7
SEZ6-targeting antibody-drug conjugate ABBV-706 in advanced small cell lung cancer and solid tumors: a phase 1 trial.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This open-label, phase 1 clinical trial assessed the safety, tolerability, pharmacokinetics, immunogenicity, and antitumor activity of ABBV-706, a SEZ6-targeting antibody-drug conjugate, in 288 patients with advanced solid tumors, with a focus on 124 relapsed/refractory (R/R) small cell lung cancer (SCLC) patients. ABBV-706 was administered intravenously every 3 weeks, with safety outcomes highlighting anemia (61%) and fatigue (38%) as the most common treatment-related adverse events in the monotherapy cohort, and grade 3 or higher adverse events in 61% of R/R SCLC patients. Efficacy data showed an objective response rate of 52% in R/R SCLC, with comparable ORRs (56% and 59%) between 1.8 mg/kg and 2.5 mg/kg doses and median overall survival of 12.4 months at 1.8 mg/kg. The study concluded 1.8 mg/kg as the recommended phase 2 dose based on safety and efficacy.
10.1038/s41591-026-04452-0
Savolitinib in MET-amplified gastric or gastroesophageal junction adenocarcinoma: a phase 2 trial.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This open-label, multicenter phase 2 clinical trial evaluated the efficacy and safety of savolitinib, an oral MET inhibitor, in patients with MET-amplified, locally advanced or metastatic gastric or gastroesophageal junction cancer in China. A total of 110 patients were enrolled across exploratory (n=45) and pivotal (n=65) phases, receiving oral savolitinib after progressing on prior systemic therapies; the pivotal phase required MET gene copy number ≥10. The pivotal phase yielded an objective response rate (ORR) of 32.3% (95% CI: 21.2-45.1%), meeting the prespecified efficacy threshold, with grade ≥3 treatment-related adverse events in 34.5% of all participants and one (0.9%) treatment-related death. The study concludes that savolitinib displays promising antitumor activity and manageable safety in this population, meriting further randomized trials.
10.1038/s41591-026-04459-7
Tumor-targeted interferon-α gene therapy for glioblastoma: a phase 1 trial.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This phase 1/2a dose-escalation study evaluated Temferon, a genetically engineered autologous stem cell transplant delivering interferon-α2 to the tumor microenvironment in 24 newly diagnosed glioblastoma patients with unmethylated MGMT promoter. The primary endpoint was safety and tolerability within 90 days post-infusion; no dose-limiting toxicities occurred up to the highest dose tested. Median overall survival was 16.7 months and progression-free survival was 8.1 months from diagnosis, with most patients maintaining good performance status. The authors conclude Temferon is a safe and tolerable immunotherapeutic strategy for newly diagnosed glioblastoma.
10.1038/s41591-026-04419-1
Neoadjuvant Sacituzumab Govitecan in Patients With Muscle-Invasive Bladder Cancer: Primary Results of the SURE-01 Trial.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This phase II, single-arm SURE-01 trial evaluated neoadjuvant sacituzumab govitecan (SG) in patients with cT2–T4aN0M0 muscle-invasive bladder cancer ineligible for or refusing neoadjuvant chemotherapy, administering four 3-week cycles (initially 10 mg/kg on days 1 and 8, then amended to 7.5 mg/kg) followed by radical cystectomy (RC); baseline tumors underwent transcriptome-wide and genomic profiling. Among 44 treated, two early deaths (one treatment-related) prompted dose reduction and neutropenia prophylaxis; subsequent grade 3–4 treatment-related adverse events occurred in 5 patients (13.9%). In the intention-to-treat population, the protocol-defined ypT0N0 rate was 9.1% (95% CI, 2.5–21.7), the overall ypT0N0-x rate was 29.5% (95% CI, 16.7–45.2), and 24-month event-free survival was 71.4% (95% CI, 58–87.8); nonluminal subtypes showed higher ypT0 (46% vs 14% luminal). The study concludes SG at 7.5 mg/kg is active with manageable safety and supports TROP2 targeting; lower TOP1 expression correlated with longer EFS.
10.1200/JCO-26-00142
A Randomized Phase III Trial of Anthracyclines Followed by Taxane versus Taxane Plus Carboplatin as (Neo)Adjuvant Therapy in Patients with Triple-Negative Breast Cancer: KCSG BR 15-1 PEARLY Trial.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
The PEARLY trial, a randomized phase 3 study, evaluated the efficacy and safety of adding carboplatin to standard anthracycline/taxane chemotherapy in 868 patients with early-stage triple-negative breast cancer (TNBC) across 22 institutions in Korea. Patients were randomized to receive either standard therapy (doxorubicin/cyclophosphamide followed by taxane) or the same regimen plus carboplatin, with primary endpoint of event-free survival (EFS). At median 57.2-month follow-up, carboplatin significantly improved EFS (HR=0.67, 95% CI: 0.49-0.92, P=0.012), with 5-year EFS rates increasing from 75.1% to 82.3% (absolute 7.2% difference), though secondary endpoints (OS, IDFS, DRFS) showed non-significant trends favoring carboplatin. The study concluded that carboplatin addition significantly improved EFS in early TNBC despite higher grade ≥3 adverse events (74.7% vs 56.7%), with maintained quality of life supporting its favorable risk-benefit profile.
10.1016/j.annonc.2026.05.703
MAGE-A4/MAGE-A8-targeted TCR-based bispecific T cell engager in recurrent and/or refractory solid tumors: a phase 1 trial.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This phase 1 prespecified interim analysis evaluated IMA401, a novel TCR-based bispecific T cell engager, in 61 patients with recurrent and/or refractory solid tumors, administered intravenously with or without pembrolizumab. The primary focus was maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D), with secondary endpoints including safety, antitumor activity, and pharmacokinetics. The MTD was not reached, RP2D was determined as 1-2 mg biweekly, and treatment-related adverse events were primarily grade 1-2 and manageable. Efficacy-evaluable population ORR was 14% (8/56); at RP2D, ORR was 20% (8/41), with the largest subgroup—head and neck cancer—showing 29% (4/14) response and a median response duration of 8.8 months.
10.1038/s41591-026-04455-x
Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy in advanced squamous non-small-cell lung cancer (HARMONi-6): interim overall survival analysis of a randomised, double-blind, phase 3 trial in China.
LANCET · Q1 JOURNAL - RANK #1/332TOP-TIER
HARMONi-6 is a randomized, double-blind, phase 3 trial at 50 Chinese hospitals comparing ivonescimab plus paclitaxel/carboplatin (four cycles) followed by ivonescimab maintenance versus tislelizumab plus the same chemotherapy and tislelizumab maintenance in previously untreated advanced squamous NSCLC. 532 patients were randomized (266/266), median age 64 (IQR 59–69), 93% male; the prespecified interim overall survival analysis was conducted after 204 deaths with a median follow-up of 21.4 months. Ivonescimab improved median overall survival to 27.9 months (95% CI 27.89–NE) versus 23.7 months (20.11–NE) with tislelizumab (HR 0.66, 95% CI 0.50–0.87; p=0.0017), with grade ≥3 treatment-related adverse events in 69% vs 59% and grade ≥3 hemorrhage in 3% vs 1%. Investigators concluded ivonescimab plus chemotherapy confers a statistically significant and clinically meaningful overall survival benefit as first-line therapy in advanced squamous NSCLC.
10.1016/S0140-6736(26)00966-9
Amivantamab in recurrent/metastatic HNSCC after checkpoint inhibitor and chemotherapy: pivotal results from the phase 1b/2 OrigAMI-4 study.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This multicenter phase 1b/2 OrigAMI-4 trial prospectively evaluated subcutaneous amivantamab, an EGFR-MET bispecific antibody, in 102 patients with recurrent or metastatic head and neck squamous cell carcinoma who had progressed after PD-(L)1 inhibitor and platinum-based chemotherapy. Participants received amivantamab every three weeks; efficacy was measured by RECIST v1.1 with blinded independent central review, and secondary endpoints included duration of response, progression-free survival, overall survival, and safety. The study achieved a 42 % objective response rate (95 % CI 32–52 %), including 15 % complete responses; median duration of response was not reached, with 56 % ongoing ≥6 months, while median PFS and OS were 6.8 months (95 % CI 5.2–8.3) and 12.5 months (95 % CI 10.2–16.8), respectively. Adverse events were consistent with prior experience, treatment-related discontinuations were 8 %, and investigators conclude amivantamab provides greater antitumor activity than historical paclitaxel or cetuximab in this setting.
10.1200/JCO-26-01042
May 25 – Jun 01, 2026
Lorlatinib versus crizotinib as first-line treatment for advanced ALK-positive non-small cell lung cancer: 7-year update from the phase 3 CROWN study.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
The study aimed to evaluate the long-term efficacy and safety of lorlatinib versus crizotinib as first-line treatment for advanced ALK-positive non-small cell lung cancer (NSCLC) over 7 years in the phase 3 CROWN trial. A total of 296 treatment-naive patients were randomized 1:1 to receive lorlatinib (100 mg OD) or crizotinib (250 mg BID), with investigator-assessed outcomes including progression-free survival (PFS), safety, and biomarker analyses. At median follow-ups of 83.0 and 77.2 months, median PFS was not reached (NR; 68.5-NR) for lorlatinib versus 9.1 months (7.4-10.9) for crizotinib (HR 0.19; 95% CI 0.13-0.26), with 7-year PFS rates of 55% and 3%, respectively. The safety profile remained consistent with prior findings, and lorlatinib demonstrated sustained long-term disease control, suggesting potential for advanced ALK-positive NSCLC to become a chronic condition.
10.1016/j.annonc.2026.05.692
Impact of patient-reported taxane-induced peripheral neuropathy on dose reductions or worsening quality of life in Black women with breast cancer: Analysis from ECOG-ACRIN EAZ171.
CANCER-AM CANCER SOC · Q1 JOURNAL - RANK #68/326
This study, based on the prospective ECOG-ACRIN EAZ171 trial, evaluated the impact of taxane-induced peripheral neuropathy (TIPN) on dose reductions and health-related quality of life (HRQOL) in 239 Black women with breast cancer receiving (neo)adjuvant taxane. Patient-reported outcomes (PROs) assessed TIPN using the FACT-GOG/NTx scale, while HRQOL and physical function were measured using FACT-G and PROMIS PF-10a through 12 months. TIPN was common and significantly predicted taxane dose reductions, with the FACT-GOG/NTx 4-item subscale showing the strongest association (OR, 10.8; 95% CI, 4.5-25.9). Persistent TIPN was linked to worse HRQOL (OR, 5.05; 95% CI, 1.33-19.17) and physical function (OR, 5.29; 95% CI, 1.57-17.83) at 12 months; results emphasize the importance of early intervention for TIPN and its implications for equitable breast cancer treatment outcomes.
10.1002/cncr.70466
Tafasitamab plus lenalidomide and R-CHOP versus R-CHOP for first-line treatment of patients with high-risk diffuse large B-cell lymphoma (frontMIND): a global, phase 3, randomised, double-blind, placebo-controlled trial.
LANCET · Q1 JOURNAL - RANK #1/332TOP-TIER
This phase 3, randomised, double-blind, placebo-controlled multicentre clinical trial evaluated tafasitamab plus lenalidomide added to standard R-CHOP versus R-CHOP alone as first-line treatment for untreated high-risk diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL) in 899 adult patients. Patients received six 21-day cycles with stratified random assignment; progression-free survival was the primary endpoint. At median follow-up of 35.2 months, the tafasitamab-lenalidomide-R-CHOP group had a hazard ratio for progression-free survival of 0.75 (95% CI 0.59-0.96, p=0.0194) and a 2-year progression-free survival rate of 71.1% versus 62.9% for R-CHOP alone; grade 3 or higher adverse events were more frequent with tafasitamab-lenalidomide-R-CHOP (87% vs 76%). The trial concluded tafasitamab-lenalidomide-R-CHOP may offer a new first-line option, but with increased adverse event rates.
10.1016/S0140-6736(26)00866-4
First-line envafolimab plus recombinant human-endostatin in advanced non-small cell lung cancer with PD-L1 tumor proportion score ≥1% (Endouble): A multicenter, prospective, single-arm, phase 2 trial.
CANCER-AM CANCER SOC · Q1 JOURNAL - RANK #68/326
This multicenter, prospective, single-arm, phase 2 trial evaluated the efficacy and safety of envafolimab plus recombinant human endostatin (Rh-endostatin) in 33 treatment-naive advanced NSCLC patients with PD-L1-positive and no driver gene mutations. Patients received treatment every 21 days until disease progression or intolerable toxicity, with primary endpoints being objective response rate (ORR) and safety, and secondary endpoints including progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and duration of response (DOR). The ORR was 48.5% (95% CI, 30.8%-66.5%), DCR was 81.8% (95% CI, 64.5%-93.0%), median PFS was 12.3 months (95% CI, 3.1-21.5 months), and 1-year OS rate was 73.9%, with no grade 4 or 5 adverse events reported. The study concluded that the combination demonstrated favorable efficacy and tolerable toxicity in this patient population, supported by exploratory biomarker analysis showing AUC values of 0.77 for MMP1 and 0.68 for TNFRSF6B.
10.1002/cncr.70479
Accuracy of Index Lymph Node Pathology in Predicting Overall Response to Neoadjuvant Immunotherapy for Clinical Stage III Melanoma: Results From the Prospective NeoACTIVATE Arm C (NCT03554083) Substudy.
ANN SURG ONCOL · Q1 JOURNAL - RANK #39/312
This preplanned prospective substudy of the multicenter NeoACTIVATE Arm C trial evaluated whether pathology of a clipped index lymph node (ILN) predicts whole-nodal-basin response after neoadjuvant atezolizumab plus tiragolumab in resectable clinical stage III melanoma, using International Neoadjuvant Melanoma Consortium criteria and therapeutic lymph node dissection. Among 34 enrolled patients, 30 underwent TLND per protocol; 2/30 (6.7%) showed discordance (ILN pathologic complete response [pCR] but residual disease in non-ILNs), yielding an ILN pCR false-negative rate of 13.3%. In the subgroup with a single involved node at baseline (n=8), pathologic major response was 75% and concordance was 100%. The study concludes ILN pathology alone may not fully reflect basin status, advising caution in de-escalation based solely on ILN response and calling for trials of limited nodal resection.
10.1245/s10434-026-19899-1
Concordance between clinician-reported toxicities and patient-reported symptom severity in early-stage breast cancer: an analysis of the randomized phase III PANTHER trial.
ESMO OPEN · Q1 JOURNAL - RANK #36/326
This study examined concordance between clinician-reported toxicities and patient-reported symptom severity during adjuvant chemotherapy for early-stage breast cancer, using data from the randomized phase III PANTHER trial. Clinician toxicities were graded via CTCAE v3.0, and patient symptoms via EORTC QLQ-C30 and BR23 questionnaires at mid- and end-of-treatment. Among 1566 patients, weighted Cohen’s kappa showed low agreement across all six symptoms (kappa = 0.07–0.34), with highest discrepancy for fatigue (36%–54%) and pain (23%–38%). The authors concluded that concordance is poor and increases over time, advocating for routine inclusion of patient-reported assessments.
10.1016/j.esmoop.2026.107696
Extended-field intensity-modulated radiation therapy and high-dose-rate brachytherapy with concurrent chemotherapy for cervical cancer with positive para-aortic or common iliac lymph nodes: a multicenter prospective cohort study.
J GYNECOL ONCOL · Q1 JOURNAL - RANK #14/140
This multicenter prospective cohort study evaluated the efficacy and safety of extended-field intensity-modulated radiotherapy (EF-IMRT) combined with concurrent chemotherapy and high-dose-rate (HDR) brachytherapy in 204 patients with locally advanced cervical cancer and positive para-aortic (PALN) or common iliac lymph nodes (CILN). The primary endpoint was progression-free survival (PFS), with secondary endpoints including overall survival (OS), local progression-free survival (LPFS), distant metastasis-free survival (DMFS), and adverse events. The 3-year and 5-year PFS rates were 68.3% and 64.6%, respectively, while OS rates were 76.4% and 69.5%, and 5-year LPFS and DMFS were 83.1% and 70.1%. The study concluded that EF-IMRT with concurrent chemotherapy was tolerable and effective, with favorable local control and OS outcomes.
10.3802/jgo.2026.37.e114
Addition of Intravesical Recombinant BCG to Perioperative Chemo-Immunotherapy in Muscle-Invasive Bladder Cancer: Primary Analysis of the Single-Arm Phase 2 Trial SAKK 06/19.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This open-label, single-arm phase II trial (SAKK 06/19) evaluated neoadjuvant intravesical recombinant BCG (VPM1002BC) added to atezolizumab and cisplatin/gemcitabine in cT2–T4a N0–1 muscle-invasive bladder cancer, followed by radical cystectomy with lymphadenectomy. rBCG was instilled weekly for three doses beginning day 1; atezolizumab was given on day 1 for four doses; chemotherapy started day 22 for four cycles; adjuvant atezolizumab was reserved for >yT1 ypN0. Among 47 enrolled patients (95% received rBCG; 78% completed all three doses), centrally reviewed pCR was 68% (27/40; one-sided 95% CI lower bound 53%) and PaR was 83% (33/40; 95% CI 67–93); seven did not undergo surgery. Treatment-related adverse events were 42%/9%/0% (any/grade 3/grade 4) for rBCG, 55%/15%/2% for atezolizumab, and 96%/38%/17% for chemotherapy; investigators conclude high response rates warrant randomized trials.
10.1200/JCO-26-00845
Post-hoc analysis of adverse events during the EPOCH trial: reconsidering dosimetry.
EUR J NUCL MED MOL I · Q1 JOURNAL - RANK #10/212
This post-hoc analysis of the EPOCH trial examined the impact of yttrium-90 [Y]-radioembolization dosimetry on adverse events in colorectal cancer patients with liver metastases who had progressed following frontline chemotherapy. The study analyzed liver-related treatment-emergent adverse events (TEAEs) and bilirubin increases in 186 patients, reporting TEAEs in 50% of patients, grade 3 or higher TEAEs in 24%, and bilirubin increases in 14%. A theoretical model explored dosimetry parameters, finding that patients with lower fractional tumor involvement (<4.1%) were subjected to higher normal liver absorbed doses (up to 120 Gy). The analysis proposes revised dosimetry guidelines to mitigate TEAEs while maintaining therapeutic efficacy in radioembolization.
10.1007/s00259-026-07948-6
Tumor flare-like response: A novel imaging phenomenon with predictive significance in triple negative breast cancer patients undergoing neoadjuvant immuno-chemotherapy.
BREAST · Q1 JOURNAL - RANK #4/140
This ad hoc imaging analysis of a prospective phase II trial (NCT04213898; n=39) investigated tumor flare-like response (TFLR) on breast MRI in triple-negative breast cancer patients undergoing neoadjuvant immuno-chemotherapy. TFLR occurred in 74.4% of patients and completely resolved in 75.9% by treatment completion; median persistence was 152 days. Largest nodule diameter ≥9 mm independently predicted pathological complete response (pCR) in multivariable analysis (OR=7.833, 95% CI 1.260-48.701, P=.027), while TFLR presence alone did not (P=.72). The authors conclude TFLR is a frequent, reversible MRI finding and that nodule size ≥9 mm is a promising early imaging biomarker of immunotherapeutic efficacy.
10.1016/j.breast.2026.104823
Preoperative onapristone-XR in postmenopausal women with progesterone receptor-positive (PgR+)/HER2-negative early breast cancer: SOLTI-1802 ONAWA trial results.
NPJ BREAST CANCER · Q1 JOURNAL - RANK #42/326
The SOLTI-1802 ONAWA trial was a single-arm prospective clinical trial examining preoperative, extended-release onapristone (ONA-XR, 50 mg BID for 21 days) in postmenopausal women with progesterone receptor-positive (PgR+)/HER2-negative early breast cancer. The primary objective was to assess changes in tumor proliferation; ONA-XR suppressed proliferation, with a Ki-67 geometric mean change of -17.78% (CI95 -39.76% to 12.20%) and greater effect in tumors with PgR≥90% (-46.21%; CI -63.02% to -21.76%). Immunohistochemical analyses confirmed molecular pathway effects, and 60% of participants experienced adverse events. The trial concludes ONA-XR is active in suppressing early tumor proliferation, warranting further clinical evaluation.
10.1038/s41523-025-00887-9
Four-year survival outcomes with dostarlimab plus chemotherapy in mismatch repair deficient/microsatellite instability-high primary advanced or recurrent endometrial cancer in the RUBY trial.
GYNECOL ONCOL · Q1 JOURNAL - RANK #11/140
This is a prospective, randomized, double-blind, placebo-controlled Phase 3 clinical trial (RUBY, NCT03981796) evaluating dostarlimab plus carboplatin-paclitaxel (CP) versus placebo plus CP in patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer. With a median follow-up of 55.6 months, the study reports descriptive analyses of overall survival (OS) and progression-free survival (PFS), plus post-hoc conditional survival and mixture cure model (MCM) analyses to estimate curative potential. Key findings include a 66% reduction in risk of death, median PFS and OS not reached, and a 54% (95% CI 35%-72%) cure rate estimated by MCM at 4 years with dostarlimab plus CP. The authors conclude that dostarlimab plus CP demonstrates sustained remission and long-term survival benefit, suggesting potential for curative intent in this patient population.
10.1016/j.ygyno.2026.05.008
Apatinib enhances anti-PD-1 efficacy by inhibiting Exo70-mediated exosome secretion in pMMR/MSS colorectal cancer.
NPJ PRECIS ONCOL · Q1 JOURNAL - RANK #39/326
This single-arm, exploratory clinical study evaluated the efficacy of camrelizumab combined with apatinib in patients with advanced metastatic pMMR/MSS colorectal cancer who had received third-line or later treatment (NCT04067986). Results showed that apatinib significantly enhanced the therapeutic efficacy of immunotherapy, with mechanistic insights revealing reduced exosomal PD-L1 levels via inhibition of tumor-derived exosome secretion mediated by Exo70. The study provides a theoretical rationale for combining camrelizumab and apatinib in this patient population. No specific numerical efficacy results (e.g., response rates) were reported in the abstract.
10.1038/s41698-026-01518-7
AI-MIRACLE: Artificial Intelligence and MultIpaRAmetric MRI Predict CLinical OutcomEs to Neoadjuvant Immunotherapy in Patients with Muscle-invasive Bladder Cancer Undergoing Radical Cystectomy.
EUR UROL ONCOL · Q1 JOURNAL - RANK #7/133
This multi-institutional study analyzed data from 112 patients in the PURE-01 trial (NCT02736266), a prospective study evaluating neoadjuvant pembrolizumab before radical cystectomy in cisplatin-ineligible muscle-invasive bladder cancer patients. Pre- and post-immunotherapy multiparametric MRI data were processed using radiomics (pyCERR) and deep feature extraction (AI-BLADE/VGG19), with supervised machine learning (elastic net, random forest) used to predict pathological response. The post-ICI mpMRI radiomics model achieved an AUC of 0.96 for major pathological response (ypT<2N0), while a shape-based radiomics model achieved an AUC of 0.86 for pathological complete response (ypT0). The authors concluded that these imaging biomarkers provide noninvasive assessment of treatment response, potentially guiding bladder-preserving strategies before definitive surgery.
10.1016/j.euo.2026.05.006
Sacituzumab tirumotecan plus pembrolizumab versus pembrolizumab in PD-L1-positive advanced non-small-cell lung cancer (OptiTROP-Lung05): interim analysis of a randomised, open-label, phase 3 trial.
LANCET · Q1 JOURNAL - RANK #1/332TOP-TIER
The study evaluated the efficacy and safety of sacituzumab tirumotecan (sac-TMT) plus pembrolizumab versus pembrolizumab alone as first-line treatment for PD-L1-positive advanced non-small-cell lung cancer (NSCLC) in a randomized, open-label, phase 3 trial. A total of 413 patients were assigned to sac-TMT plus pembrolizumab (n=208) or pembrolizumab alone (n=205), with a median follow-up of 10.5 months. The combination therapy significantly improved progression-free survival (not reached vs 5.7 months; HR 0.35, 95% CI 0.26-0.47, p<0.0001) and showed consistent benefits across PD-L1 subgroups, though with higher grade 3+ adverse events (55% vs 31%). The study concludes that sac-TMT plus pembrolizumab may redefine first-line treatment for this patient population.
10.1016/S0140-6736(26)00968-2
Pretreatment intratumoral mature TLSs in non-clear cell renal cell carcinoma are associated with response to immunotherapy rechallenge.
J IMMUNOTHER CANCER · Q1 JOURNAL - RANK #12/183TOP-TIER
This prospective human clinical trial evaluated the efficacy, safety, and predictive markers of immune checkpoint inhibitor (ICI) rechallenge in 39 patients with metastatic non-clear cell renal cell carcinoma (nccRCC). The study reported a median progression-free survival (PFS) of 11.8 months, an objective response rate (ORR) of 13.9%, and a disease control rate (DCR) of 69.4%. Patients with a high mature intratumoral tertiary lymphoid structure (m-iTLS) score had significantly better outcomes (ORR: 50.0% vs 0.0%, PFS: 28.2 vs 5.0 months), and ICI rechallenge was well tolerated with no treatment-related deaths observed. The findings highlight potential biomarkers for predicting ICI rechallenge efficacy and emphasize the therapy’s clinical benefit in this patient population, although additional validation is required.
10.1136/jitc-2025-013526
Safety, pharmacokinetics, pharmacodynamics, and antitumor activity of cergutuzumab amunaleukin: a phase I study in patients with advanced and/or metastatic solid tumors.
ESMO OPEN · Q1 JOURNAL - RANK #36/326
This phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of cergutuzumab amunaleukin (CA) in 60 patients with advanced/metastatic CEA-positive solid tumors. The study comprised two parts: single-dose (0.1-6 mg, n=5) and multiple ascending doses (10-40 mg q2w, n=31; 6-30 mg qw, n=24), establishing an MTD of 30 mg q2w with dose-limiting toxicities including Gr4 hypophosphatemia and thrombocytopenia. Pharmacokinetics showed dose-proportional exposure (6-40 mg), and pharmacodynamics revealed preferential expansion of CD8+ T and NK cells. No objective responses were observed, but 11% (6/53) achieved stable disease (median duration 4.5 months), supporting further combination therapy development.
10.1016/j.esmoop.2026.107697
Efficacy and safety of subcutaneous and intravenous administration of atezolizumab in patients with non-small cell lung cancer, including early-stage, locally advanced or metastatic disease: Updated results of the IMscin001 and IMscin002 randomized studies.
LUNG CANCER · Q1 JOURNAL - RANK #19/108
These two randomized, prospective clinical trials (IMscin001 and IMscin002) evaluated the efficacy, safety, and immunogenicity of subcutaneous (SC) versus intravenous (IV) atezolizumab in patients with non-small cell lung cancer (NSCLC) across early-stage, locally advanced, or metastatic settings. Patients were randomized to receive either SC or IV atezolizumab every three weeks, with IMscin002 including a crossover and continuation period. Updated results show similar overall survival between groups in IMscin001 (median OS: 10.9 vs 10.1 months; hazard ratio: 1.00, 95% CI: 0.78-1.27) and 44.7% ongoing clinical benefit after cycle 16 in IMscin002. Both studies found comparable safety profiles, immunogenicity (20.0-21.1% anti-drug antibodies), and no new safety signals.
10.1016/j.lungcan.2026.109452
Early radiological response pattern predicts long-term response in patients with non-small cell lung cancer treated with immune-checkpoint inhibitors.
CANCER IMAGING · Q1 JOURNAL - RANK #40/212
This prospective study evaluated early radiological response patterns in 122 NSCLC patients treated with immune checkpoint inhibitors (ICIs) from 2019 to 2023. Imaging per iRECIST assessed early sum-of-diameters (SoD) change at 8–12 weeks. Key findings: 32.8% achieved best overall response, 47.5% durable clinical benefit (DCB); early SoD reduction predicted DCB (AUC 0.764, p>0.05) and BOR (AUC 0.701, p<0.01). The authors conclude early radiological dynamics robustly predict outcomes and outperform laboratory biomarkers.
10.1186/s40644-026-01048-2
High-dose stereotactic radiotherapy boost in the radical treatment of head and neck tumors.
RADIAT ONCOL · Q1 JOURNAL - RANK #51/212
This prospective, single-center clinical trial evaluated the efficacy and safety of combining conventionally fractionated radiotherapy with a high-dose stereotactic radiotherapy boost for the radical treatment of head and neck tumors in 28 patients. Tumor response included an 89% complete response rate, with disease progression causing five deaths, and late toxicities such as carotid blow-out syndrome and brain necrosis occurring at higher boost doses. The study found that a boost dose of 10 Gy provided promising efficacy with permissible toxicity compared to higher doses, which increased the risk of adverse events. The study was approved by a bioethics committee and registered on ClinicalTrials.gov, with findings suggesting a potential role for stereotactic boosts in optimizing head and neck cancer outcomes.
10.1186/s13014-026-02857-2
Mature Outcomes and Patterns of Failure in the Phase II FLARE-RT Trial of Biological Image-guided and Risk-Adaptive Chemoradiation for Unresectable NSCLC.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
This Phase II FLARE-RT trial evaluated the efficacy of biological image-guided and risk-adaptive chemoradiation in 49 patients with unresectable NSCLC. Participants were stratified based on FDG-PET response, receiving either 60Gy or intensified doses between 74-90Gy. After a 52.3-month median follow-up, 1- and 2-year OS rates were reported as 81.6% and 54.2%, respectively, with 1- and 2-year PFS rates of 53.1% and 40.5%. The study demonstrated durable locoregional control, identified FDG-PET metrics as predictors of progression, and highlighted a potential benefit of adjunct durvalumab in reducing distant metastases without compromising local control, supporting its use in biomarker-guided NSCLC therapy.
10.1158/1078-0432.CCR-25-2626
Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line treatment in patients with advanced gastric or gastroesophageal junction adenocarcinoma, with or without peritoneal metastases: a post-hoc analysis on RATIONALE-305 study.
ECLINICALMEDICINE · Q1 JOURNAL - RANK #11/332
This post-hoc analysis of the randomized, double-blind, phase 3 RATIONALE-305 clinical trial examined the efficacy and safety of tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line treatment in 997 patients with advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJC), including those with and without peritoneal metastases. Patients were randomized 1:1 to receive either treatment regimen until disease progression or unacceptable toxicity, with outcomes measured as overall survival (OS), progression-free survival (PFS), and safety. Results showed tislelizumab plus chemotherapy significantly improved OS versus placebo plus chemotherapy in both patient subgroups: HR 0.78 (95% CI, 0.64-0.96) for those with peritoneal metastases and HR 0.79 (95% CI, 0.65-0.95) for those without; PFS benefits were similarly observed. The safety profile was comparable across treatment arms and subgroups.
10.1016/j.eclinm.2026.103980
Intrathecal Allogeneic B7-H3-targeted CAR γδ T Cells for Leptomeningeal Metastasis from Solid Tumors: Safety, Efficacy, and Immunological Dynamics in a Phase 1 Trial.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
Phase 1 trial NCT06592092 evaluated intrathecal QH104, an allogeneic B7-H3–targeted CAR γδ T-cell therapy, in three patients with B7-H3–positive leptomeningeal metastases from lung adenocarcinoma (n=2) or triple-negative breast cancer (n=1). Patients received 3 × 10^7 cells per infusion via lumbar puncture or Ommaya reservoir; primary endpoint was clinical response, with safety, overall survival, quality of life, and PK/PD as secondary endpoints. QH104 was generally well tolerated (no grade ≥4 TRAEs; one grade 3 ICANS resolving with care), all patients achieved stable disease at days 14 and 30 with symptom improvement in two, and CSF cytology converted and remained negative to day 30 in one baseline-positive case. CAR γδ T cells persisted in CSF for at least one week with increased IFN-γ, and single-cell sequencing indicated IFN-γ–associated immune remodeling.
10.1158/1078-0432.CCR-26-0738
Long-Term Analysis of NRG Oncology RTOG 0539: A Phase II Trial of Observation for Low-Risk Meningioma and Radiotherapy for Intermediate- and High-Risk Meningioma.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
The study presents a prospective phase II trial (NRG Oncology RTOG 0539) on risk-adapted radiotherapy for WHO grade 1-3 meningioma patients. The primary objective was to assess the outcomes of observation for low-risk patients and radiotherapy for intermediate- and high-risk cohorts using a Kaplan-Meier analysis to estimate progression-free survival (PFS) and overall survival (OS) over a median follow-up of 11-12 years. Key results include 10-year PFS and OS rates of 85.2%/94.1% (low-risk), 72.2%/84.7% (intermediate-risk), and 42.5%/51.1% (high-risk), with grade 3+ radiotherapy toxicity rates of 9.6% and 15.1% in intermediate- and high-risk cohorts, respectively. The findings demonstrate the value of observation for low-risk patients and radiotherapy for higher-risk patients, while providing benchmarks for future trials.
10.1200/JCO-25-01441
Osimertinib plus selumetinib in patients with EGFR-mutated advanced NSCLC with BRAF alterations post-progression on first-line osimertinib: ORCHARD.
EUR J CANCER · Q1 JOURNAL - RANK #45/326
The ORCHARD study was a phase II, biomarker-matched, prospective clinical trial evaluating osimertinib plus selumetinib in 16 patients with EGFR-mutated advanced non-small cell lung cancer (NSCLC) with BRAF alterations after progression on first-line osimertinib. Patients received osimertinib (80 mg daily) and selumetinib (75 mg twice daily) until disease progression or intolerable toxicity, with primary and secondary endpoints including objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. The ORR was 7% (80% CI < 1-25), median PFS was 3.4 months (95% CI 1.3-5.4), median OS was 14.0 months (95% CI 6.2-not calculable), and 69% experienced grade ≥3 adverse events. The combination showed minimal efficacy and a safety profile consistent with known drug effects, concluding further evaluation is not warranted.
10.1016/j.ejca.2026.116807
Sequential chemo-immunotherapy followed by standard versus reduced thoracic radiotherapy for older and/or frail stage III non-small-cell lung cancer: A randomized open-label cohort trial.
PLOS MED · Q1 JOURNAL - RANK #13/332
This phase II randomized, open-label, two-cohort trial evaluated sequential chemo-immunotherapy followed by standard versus reduced thoracic radiotherapy (RT) intensity in 56 older and/or frail patients with stage III NSCLC ineligible for concurrent chemoradiotherapy (cCRT). The 1-year progression-free survival (PFS) was 84.3% for the standard RT group and 70.7% for the reduced RT group in the intention-to-treat set. Grade 3/4 adverse events occurred in 71.4% of standard RT patients and 53.6% of reduced RT patients, with grade 5 AEs in 10.7% and 3.6%, respectively. The results indicate that reduced RT combined with sequential chemo-immunotherapy is a feasible option, though limitations such as small sample size and non-comparative design necessitate further randomized trials.
10.1371/journal.pmed.1005111
Zanidatamab with and without Tislelizumab in HER2-Positive Gastroesophageal Cancer.
NEW ENGL J MED · Q1 JOURNAL - RANK #2/332TOP-TIER
This open-label, randomized phase 3 trial compared first-line zanidatamab plus chemotherapy with or without tislelizumab versus trastuzumab plus chemotherapy in HER2-positive advanced gastroesophageal adenocarcinoma. Patients were assigned 1:1:1; primary endpoints were progression-free survival (PFS) and overall survival (OS); median follow-up was 25.9 months. PFS was longer with zanidatamab regimens (12.4 months in both arms) than with trastuzumab (8.1 months): HR 0.63 (95% CI 0.51–0.78; P<0.001) for zanidatamab+tislelizumab and 0.65 (0.52–0.81; P<0.001) for zanidatamab. OS improved with zanidatamab+tislelizumab (26.4 vs 19.2 months; HR 0.72, 95% CI 0.57–0.90; P=0.004) but not significantly with zanidatamab alone (24.4 months; HR 0.80; P=0.06); grade ≥3 adverse events occurred in 83.3%, 73.8%, and 74.5%, with diarrhea in 24.8%, 20.0%, and 12.9%, respectively.
10.1056/NEJMoa2517729
Adjuvant chemoradiotherapy versus completion total mesorectal excision after local excision for early rectal cancer (TESAR): a multicentre, randomised, controlled, phase 3, non-inferiority trial.
LANCET GASTROENTEROL · Q1 JOURNAL - RANK #2/147TOP-TIER
This multicentre, open-label, randomised, controlled, phase 3 non-inferiority trial (TESAR) compared adjuvant chemoradiotherapy (25 x 1.8 Gy with capecitabine) to completion total mesorectal excision (cTME) in 202 patients with locally excised high-risk pT1 and low-risk T2 rectal cancer. The primary endpoint was 3-year locoregional recurrence (non-inferiority margin 7%). Estimated 3-year recurrence was 5.0% after chemoradiotherapy vs. 1.1% after cTME, with a non-significant difference (3.9%, 90% CI 0.0-9.4; p=0.16), failing to demonstrate non-inferiority. However, unsalvageable recurrence rates were low (1.3% vs. 0.0%), and 3-year stoma rates were significantly lower after chemoradiotherapy (2.6% vs. 45.4%; p<0.0001), with comparable overall survival. The authors conclude that adjuvant chemoradiotherapy challenges cTME as standard of care due to reduced morbidity and stoma rates, despite not meeting formal non-inferiority for locoregional recurrence.
10.1016/S2468-1253(26)00109-3
Efficacy and safety of durcabtagene autoleucel in a phase 1 trial for patients with relapsed/refractory multiple myeloma.
SCI TRANSL MED · Q1 JOURNAL - RANK #3/195TOP-TIER
Part A of a phase 1 trial (NCT04318327) prospectively evaluated durcabtagene autoleucel, a rapidly manufactured BCMA-directed CAR T therapy, in 55 patients with relapsed/refractory multiple myeloma with safety as the primary objective and efficacy/feasibility as secondary endpoints. Patients received a single infusion at one of four flat target doses after a median 24-day vein-to-vein time. The overall response rate was 98%, stringent complete response rate 55%, and minimal residual disease negativity 80% among evaluable patients (35/44); no unexpected safety findings or delayed neurotoxicity were observed. Immunophenotyping/transcriptomics showed a preserved stem-like phenotype, supporting initiation of a phase 2 trial (NCT05172596).
10.1126/scitranslmed.adx1799
Safety analyses of the INAVO120 randomised phase III trial of inavolisib or placebo with palbociclib-fulvestrant in patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative, endocrine-resistant advanced breast cancer.
ESMO OPEN · Q1 JOURNAL - RANK #36/326
This randomized phase III clinical trial evaluated the safety profile of inavolisib plus palbociclib-fulvestrant versus placebo plus palbociclib-fulvestrant in patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative, endocrine-resistant advanced breast cancer. Active interventions included defined oral and intramuscular dosing schedules, with adverse events graded per NCI CTCAE v5.0 and managed by supportive medications. Hyperglycaemia led to inavolisib dose interruptions in 27.2% of patients and discontinuations in 0.6%, with similar reporting for rash, stomatitis, and diarrhoea; management strategies involved clinically indicated therapy such as metformin, hydrocortisone, dexamethasone mouthwash, and loperamide. The study concluded the safety profile was generally consistent, manageable, and tolerable, and adverse events were reversible with appropriate treatment.
10.1016/j.esmoop.2026.107735
Blood Pressure Changes After Oral 5-Aminolevulinic Acid Hydrochloride Administered 4-8 h Before TURBT: An Additional Analysis of a Phase III Study (SPP2C102).
LIFE-BASEL · Q1 JOURNAL - RANK #22/107
This prospective phase III study assessed blood pressure changes and hypotension-related adverse drug reactions after oral 5-aminolevulinic acid hydrochloride administration in patients undergoing transurethral resection of bladder tumor (TURBT). Blood pressure was monitored for 24 hours post-dose, with hypotension-related ADRs assessed within 14 days, and photodynamic diagnosis sensitivity compared under blue versus white light (95.3% vs. 61.1%, p < 0.001). The nadir in blood pressure occurred 2 hours after dosing, with hypotension (≤ 80 mmHg) observed in 2.1% of patients—much lower than prior retrospective studies—and 25.5% experiencing non-serious, resolved ADRs. The study concludes the lower incidence of hypotension may result from protocol-controlled exclusion criteria and medication restrictions.
10.3390/life16050819
Phase 1 evaluation of patients with newly diagnosed glioblastoma treated with radiation, nivolumab, and IDO1 enzyme inhibitor BMS-986205.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
This phase 1 trial evaluated the safety and tolerability of radiotherapy (RT) combined with nivolumab and the IDO1 enzyme inhibitor BMS-986205 in newly diagnosed glioblastoma (GBM) patients. The study included two cohorts: MGMT unmethylated patients (Cohort A) receiving RT, nivolumab, and escalating BMS-986205 doses, and MGMT methylated patients (Cohort B) receiving BMS-986205 at 25mg daily with RT, nivolumab, and temozolomide (TMZ). Treatment-related adverse events were mostly lower grade, with dose-limiting toxicities (grade 3 transaminase increases) observed in 2 patients at 50mg and 3 patients at 100mg BMS-986205, leading to a recommended phase 2 dose of 50mg daily. The study concluded that the combination therapy is safe and established a recommended dose for further evaluation in MGMT-unmethylated GBM patients.
10.1158/1078-0432.CCR-26-1124
Sensitivity to endocrine therapy index predicts benefit from weekly adjuvant paclitaxel for hormone receptor-positive breast cancer in the GEICAM/9906 trial.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
This prospective-retrospective biomarker study within the GEICAM/9906 trial (NCT00129922) compared adjuvant FEC followed by weekly paclitaxel versus six cycles of FEC in lymph node-positive breast cancer. Among 567 evaluable HR+/HER2- tumor samples, the SETER/PR index was measured with a pre-specified cutpoint (<0.75), identifying 92 tumors (16.2%) with low endocrine transcriptional activity. A significant interaction between SETER/PR status and treatment on distant recurrence-free interval was observed (p=0.046), with low-index patients benefiting from paclitaxel (HR 0.46; 95% CI, 0.22-0.95; p=0.035), while no benefit was seen for high-index patients (HR 1.02; 95% CI, 0.70-1.47; p=0.931). The authors conclude that low endocrine transcriptional activity independently validates the SETER/PR index as a predictive biomarker for paclitaxel benefit in HR+/HER2- breast cancer.
10.1158/1078-0432.CCR-26-0177
Durvalumab Plus Paclitaxel, with or without Capivasertib or Oleclumab, in Patients with Locally Advanced/Metastatic Triple-Negative Breast Cancer.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
This phase Ib/II, multiarm, platform study (BEGONIA) evaluated durvalumab plus paclitaxel with or without capivasertib or oleclumab as first-line treatment for locally advanced unresectable/metastatic triple-negative breast cancer (mTNBC). The primary objective was safety and tolerability; secondary endpoints included objective response rate (ORR). Confirmed ORR was 56.5% for durvalumab plus paclitaxel (n=23), 54.8% for capivasertib combination (n=31), and 51.5% for oleclumab combination (n=33). The authors conclude that durvalumab plus paclitaxel shows clinical activity, but adding capivasertib or oleclumab provided no substantial additional benefit.
10.1158/1078-0432.CCR-25-4417
Molecular classification and association with survival outcomes in high-intermediate and high-risk early-stage endometrial cancers: Ancillary analysis of GOG-0249.
GYNECOL ONCOL · Q1 JOURNAL - RANK #11/140
The study aimed to determine whether mismatch repair (MMR) and p53 expression predict recurrence-free survival (RFS) and overall survival (OS) in early-stage endometrial cancer (EC) patients treated with vaginal cuff brachytherapy plus chemotherapy (VCB/C) versus pelvic radiation therapy (RT). In the GOG-0249 trial, 601 patients with high-intermediate risk (HIR) early-stage EC were randomized to VCB/C or pelvic RT, with molecular subgroups analyzed by immunohistochemistry. Five-year RFS and OS were worse in patients with p53abn cancers (58.7% RFS, HR=4.0; 70.7% OS, HR=9.4) and dMMR cancers (74.4% RFS, HR=1.8; 84.3% OS, HR=3.0) compared to p53wt (83.4% RFS, 95.3% OS). Molecular classification was prognostic for survival, but treatment outcomes did not differ by molecular subgroup, highlighting the need for novel therapies for high-risk patients.
10.1016/j.ygyno.2026.05.013
NeoCircle: pre- and post-operative circulating tumor DNA dynamics predicts survival in neoadjuvant-treated early breast cancer.
EMBO MOL MED · Q1 JOURNAL - RANK #21/195
The study evaluated the predictive value of circulating tumor DNA (ctDNA) dynamics in 136 early breast cancer patients undergoing neoadjuvant treatment (NAT) from the prospective SCAN-B study (NCT02306096). Using a personalized tumor-informed digital PCR approach, baseline ctDNA detection was 89.7%, with end-NAT positivity (21.4%) and non-response (13.1%) significantly predicting disease recurrence and death, outperforming pathologic complete response. Post-operative ctDNA detection was associated with distant recurrence (median lead-time 13.8 months). The findings support the clinical utility of structural variants as a minimal residual disease analyte in breast cancer.
10.1038/s44321-026-00447-z
Amivantamab plus chemotherapy vs. chemotherapy as first-line treatment in Chinese mainland patients with EGFR exon 20 insertion non-small cell lung cancer: Subgroup analysis of the randomized PAPILLON trial.
CHINESE MED J-PEKING · Q1 JOURNAL - RANK #23/332
This subgroup analysis of the phase 3 PAPILLON trial assessed amivantamab with carboplatin-pemetrexed versus carboplatin-pemetrexed alone in treatment-naïve Chinese mainland patients with advanced EGFR exon 20 insertion non-small cell lung cancer. In this randomized, open-label study, 87 patients were allocated to amivantamab plus chemotherapy (n = 39) or chemotherapy (n = 48); progression-free survival (PFS) by blinded independent central review was the primary endpoint. Median PFS was 12.3 months (95% CI 7.0-NE) with the combination versus 6.7 months (95% CI 4.2-8.6) with chemotherapy (HR 0.47, 95% CI 0.26-0.85, p = 0.0109); objective response rates were 71.8% vs 48.9% (OR 2.46, 95% CI 1.01-5.98). No new safety signals emerged and no patients discontinued amivantamab for toxicity, supporting the regimen as a first-line option for this molecularly defined NSCLC population.
10.1097/CM9.0000000000004134
Systematic photodynamic therapy for concurrent cervical-vaginal high-grade squamous intraepithelial lesion: a series of eight cases.
LASER MED SCI · Q1 JOURNAL - RANK #78/312
This study evaluated the efficacy of Hiporfin-based photodynamic therapy (PDT) as a non-invasive treatment option for concurrent cervical-vaginal high-grade squamous intraepithelial lesion (HSIL). Hiporfin 2.0 mg/kg was administered intravenously, followed by 630-nm red laser irradiation 48-72 hours later, to eight patients with pathologically confirmed concurrent lesions. At 3-6 months, the complete response rate was 75.0% (6 of 8), while two partial responders achieved CR after additional therapy. These preliminary results suggest Hiporfin-PDT is a feasible and potentially effective option for concurrent cervical-vaginal HSIL.
10.1007/s10103-026-04896-3
Fibroblast growth factor receptor inhibition for succinate dehydrogenase-deficient gastrointestinal stromal tumors: a phase 2 trial.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This prospective, single-arm phase 2 trial evaluated the pan-FGFR inhibitor rogaratinib in advanced SDH-deficient gastrointestinal stromal tumors, with a primary objective of objective response rate and secondary endpoints of progression-free survival (PFS) and safety; exploratory serial biopsies assessed FGF3/FGF4, FGFRs, whole-exome sequencing, and PK/PD. Twenty-four patients were treated; 10 achieved partial responses for an ORR of 41.7%. Median PFS was 31.0 months (95% CI 20.2–not reached) and 1-year PFS was 77.4% (95% CI 61.7–97.1). Toxicities were manageable (hyperphosphatemia, fatigue, diarrhea), phosphorus elevations indicated FGFR1 target engagement, and sequencing confirmed SDHx alterations, supporting FGFR inhibition as an effective targeted therapy in this epigenetically driven GIST subtype (NCT04595747).
10.1038/s41591-026-04376-9
Neoadjuvant Durvalumab ± Tremelimumab in Combination With Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin in Muscle-Invasive Bladder Carcinoma: Results of the Phase I/II NEMIO Study.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
Using a multicenter, randomized, noncomparative phase II design, the study aimed to evaluate efficacy and safety of neoadjuvant ddMVAC combined with durvalumab or durvalumab plus tremelimumab in muscle-invasive bladder carcinoma. Participants received ddMVAC once every two weeks for four cycles plus two doses of immunotherapy prior to radical cystectomy. The overall Bayesian posterior mean pathologic complete response (pCR) rate was 48.70% (doublet) versus 46.27% (triplet), with higher pCR in PD-L1-high tumors (68.25% vs 33.49%). Both regimens showed favorable early survival outcomes, although the triplet presented higher toxicity, indicating ddMVAC plus durvalumab as a promising neoadjuvant option for future comparative trials.
10.1200/JCO-25-03045
PiggyBac-engineered membrane-bound IL-7 TILs combined with anti-PD-1 antibody demonstrates efficacy in recurrent ovarian cancer: a first-in-human phase 1 trial.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
This first-in-human phase 1 clinical trial evaluated the safety, tolerability, and efficacy of the GC203 regimen, which combines piggyBac-engineered membrane-bound IL-7 (mbIL-7) autologous tumor-infiltrating lymphocytes (TILs) with an anti-PD-1 antibody, in 18 heavily pretreated recurrent ovarian cancer (rOC) patients. Participants underwent lymphodepletion followed by GC203 infusion, and treatment-related adverse events were predominantly transient and hematologic (57% had grade ≥3 lymphopenia and neutropenia). Results showed an unconfirmed objective response rate (ORR) of 33.3% and a disease control rate (DCR) of 83.3%, with a median progression-free survival (PFS) of 7.2 months and overall survival (OS) of 17.1 months. Exploratory analysis revealed that the Morisita Overlap Index (MOI) predicted treatment response, supporting further development of GC203 for rOC management.
10.1158/1078-0432.CCR-25-4130
Overall survival and long-term safety of olaparib maintenance in patients with platinum-sensitive relapsed ovarian cancer: final analyses of phase III L-MOCA trial.
J OVARIAN RES · Q1 JOURNAL - RANK #6/42
This study aimed to evaluate overall survival and long-term safety of olaparib maintenance therapy in Asian patients with platinum-sensitive recurrent ovarian cancer (PSROC). As a prospective, open-label, single-arm, Phase IIIb clinical trial, it followed patients taking oral olaparib (300 mg twice daily) until disease progression or unacceptable toxicity, with a median follow-up of 73.4 months. The median overall survival (mOS) reached 51.0 months (95% CI: 42.7–56.1), with subgroup analysis showing mOS of 64.4 months (BRCA-mutated) and 40.9 months (BRCA wild-type). Long-term safety data revealed no new safety concerns, with 1.3% experiencing myelodysplastic syndrome or acute myeloid leukemia (MDS/AML).
10.1186/s13048-026-02144-4
Durvalumab plus anlotinib versus durvalumab alone as maintenance treatment in extensive-stage small-cell lung cancer (DURABLE): a multicenter, randomized, phase II trial and biomarker analysis.
NAT COMMUN · Q1 JOURNAL - RANK #10/135TOP-TIER
The DURABLE trial was a prospective, multicenter, randomized phase II study (NCT04985851) comparing durvalumab plus anlotinib versus durvalumab alone as maintenance therapy in 66 patients with extensive-stage small-cell lung cancer (ES-SCLC) after first-line durvalumab plus platinum-etoposide chemotherapy. The primary endpoint, progression-free survival (PFS), showed a median of 5.4 months for the durvalumab plus anlotinib group versus 1.9 months for durvalumab alone (HR=0.64; 80% CI, 0.44-0.94; p=0.12), with grade 3-4 adverse events occurring in 24.2% and 12.5% of patients, respectively. Biomarker analysis indicated improved outcomes with combined therapy in patients with impaired antigen presenting capacity or low bTMB. The study concludes that durvalumab plus anlotinib is a potentially effective and well-tolerated maintenance option for ES-SCLC.
10.1038/s41467-026-73562-7
Pathological Outcomes After Uncertain Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer.
ANN SURG · Q1 JOURNAL - RANK #10/312
This study investigated pathological outcomes in patients with esophageal cancer exhibiting uncertain tumor response after neoadjuvant chemoradiotherapy (nCRT) within the SANO trial. It included 272 patients with residual tumor suspicion at restaging 4-12 weeks after nCRT, of which 205 underwent esophagectomy: 15% (95% CI 10-20) had a complete pathological response. Non-traversable lesions were associated with the highest complete pathological response rate at 26% (95% CI 17-37), rising to 33% (95% CI 21-48) for those with squamous cell carcinoma. The study concludes that esophagectomy is recommended for most patients with uncertain tumor responses, given that 85% still had residual disease, though non-traversable lesion subgroup outcomes warrant nuanced clinical decision-making.
10.1097/SLA.0000000000007101
Gemcitabine and nab-paclitaxel with or without the VDR agonist paricalcitol for metastatic pancreatic cancer: a randomized, multiarm, run-in phase trial.
NAT CANCER · Q1 JOURNAL - RANK #11/326TOP-TIER
This randomized, multiarm, run-in phase trial evaluated the safety and pharmacodynamic effects of adding the VDR agonist paricalcitol to gemcitabine and nab-paclitaxel (GA) in 36 patients with metastatic pancreatic cancer. Patients were randomized to GA plus placebo, GA plus intravenous paricalcitol, or GA plus oral paricalcitol, with pretreatment and on-treatment tumor biopsies analyzed. Paricalcitol was safely administered, though 42% of oral paricalcitol recipients experienced grade 2-4 hypercalcemia requiring dose reduction. On-treatment biopsies showed decreased αSMA+ fibroblasts, altered fibroblast VDR activation, increased CD8+ T cell density and spatial colocalization with tumor cells, and VDR expression predicted tumor response in paricalcitol arms.
10.1038/s43018-026-01165-8
Pembrolizumab plus high-dose IL-2 in advanced clear cell renal cell carcinoma: six-year survival outcomes and molecular signatures from a phase 2 trial.
NAT COMMUN · Q1 JOURNAL - RANK #10/135TOP-TIER
This single-arm phase 2 trial evaluated a fixed-duration regimen of pembrolizumab plus high-dose IL-2 in 26 treatment-naive patients with advanced clear cell renal cell carcinoma. The primary objectives of safety and response were previously met, with the overall response rate exceeding the 45% threshold. At a median follow-up of 76.4 months, the objective response rate was 73%, including 42% complete responses, median overall survival exceeded 84 months, and median progression-free survival was 19.3 months. The authors conclude that this immunotherapy combination yields durable responses and a prolonged treatment-free interval without high-grade toxicities.
10.1038/s41467-026-73336-1
Sequential versus concurrent neoadjuvant immunochemotherapy in locally advanced esophageal squamous cell carcinoma: a randomized, controlled, open-label, phase 2 trial (HCHTOG1906).
FRONT IMMUNOL · Q1 JOURNAL - RANK #32/183
This open-label, phase II randomized controlled trial (HCHTOG1906) evaluated sequential versus concurrent neoadjuvant immunochemotherapy in 70 patients with resectable locally advanced esophageal squamous cell carcinoma. Patients were randomized 1:1 to sequential (paclitaxel/cisplatin day 1, toripalimab day 3) or concurrent (all drugs day 1) regimens. The overall pathological complete remission (pCR) rate was 22.2% (12/54), with no significant difference between groups (17.8% vs. 26.9%, P=0.636); however, the concurrent group had significantly higher nausea and diarrhea and more treatment-related deaths (5 vs. 1). There were no significant differences in overall survival (P=0.780) or disease-free survival (P=0.632), leading to the conclusion that while efficacy was similar, concurrent administration increased toxicity and fatal adverse events.
10.3389/fimmu.2026.1770662
May 18 – May 25, 2026
First-Line Pembrolizumab Plus Chemotherapy for Advanced Biliary Tract Cancer: China Subgroup Analysis of the Randomized Phase 3 KEYNOTE-966 Study.
ADV THER · Q1 JOURNAL - RANK #82/352
This randomized, double-blind, phase 3 Chinese subgroup analysis of the global KEYNOTE-966 trial assessed first-line pembrolizumab 200 mg every 3 weeks plus gemcitabine/cisplatin versus placebo plus gemcitabine/cisplatin in 158 adults with previously untreated advanced biliary tract cancer. After a median follow-up of 20.5 months, median overall survival was 14.1 months for pembrolizumab and 9.9 months for placebo (HR 0.74, 95% CI 0.51-1.08); median progression-free survival was 5.6 versus 5.7 months (HR 0.83). Objective response rate reached 36.0% versus 28.9%, and median duration of response was 10.2 versus 5.7 months, respectively. Grade 3/4 treatment-related adverse events occurred in 71.6% and 70.7% of patients, with no treatment-related deaths; authors conclude pembrolizumab added to chemotherapy yields clinically meaningful survival improvement and acceptable safety in Chinese patients with advanced biliary tract cancer.
10.1007/s12325-026-03578-4
Phase 1/2 study of a WT1 peptide-dosing emulsion in pediatric patients with recurrent/refractory diffuse intrinsic pontine glioma, glioblastoma, or anaplastic astrocytoma.
EUR J CANCER · Q1 JOURNAL - RANK #45/326
This first-in-child phase 1/2 clinical trial prospectively evaluated a WT1 peptide vaccine in 18 pediatric patients with recurrent/refractory DIPG, glioblastoma, or anaplastic astrocytoma. Patients received intradermal injections, with 3.5 mg determined as the phase 2 dose after no dose-limiting toxicities in phase 1 (n=4). The primary endpoint, 9-month overall survival, was 44.4% (90% CI: 24.4-65.9) for all patients and 27.3% (90% CI: 7.9-56.4) for DIPG patients, with median OS of 5.4 months for DIPG; the vaccine was not statistically effective as the lower CI did not exceed the prespecified 20% threshold, though WT1-specific immune responders showed significantly longer median OS (9.9 vs. 4.9 months, p=0.024). The authors concluded the vaccine was well tolerated and induced immune responses warranting further development. (NCT02750891)
10.1016/j.ejca.2026.116808
Testosterone and docetaxel treatment effect on mortality risk in nonmetastatic high-risk prostate cancer: A predictive biomarker analysis.
CANCER-AM CANCER SOC · Q1 JOURNAL - RANK #68/326
This study assessed whether baseline testosterone modifies the mortality benefit of adding docetaxel to radiation therapy (RT) and androgen deprivation therapy (ADT) in nonmetastatic high-risk prostate cancer, using post-hoc analyses of two randomized trials. A discovery cohort (n=255; median age 65; median follow-up 10.4 years) and a validation cohort (n=563; median age 66; median follow-up 10.6 years) were analyzed with multivariable Cox models including a treatment-by-testosterone interaction and adjustments for age, T category, Gleason score, PSA, percent positive cores, and performance status. Randomization to RT+ADT+docetaxel significantly reduced all-cause mortality in patients with normal, but not low, testosterone, with significant interactions in both cohorts (p=0.048; p=0.042); benefit was most evident with PSA >20 ng/mL, T3/4 disease, or Gleason 9/10. The authors conclude normal testosterone predicts mortality reduction from adding docetaxel, supporting testosterone group as a predictive biomarker.
10.1002/cncr.70469
Autologous T Cell Antigen Coupler Targeting HER2 (TAC01-HER2) in Advanced or Metastatic Solid Tumors.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This phase 1, first-in-human, open-label dose-escalation and dose-expansion trial evaluated TAC01-HER2, an autologous T-cell antigen-coupler therapy targeting HER2, in 23 patients with advanced or metastatic HER2-positive solid tumors. Patients received escalating doses up to the recommended phase 2 dose of 6–8 × 10⁶ cells/kg; safety (primary) and preliminary antitumor activity were assessed through adverse-event monitoring and RECIST responses. Treatment-related cytokine release syndrome occurred in 60.9 % of patients, anemia and elevated ALT in 21.7 % each; no treatment-related deaths or discontinuations occurred. Among 18 evaluable patients, disease control rate was 61.1 %, with two partial responses in nine gastric/GEJ cancer patients, median progression-free survival 2.6 months (0.8–12.4) and 6-month overall survival 57.9 % (95 % CI 36.3–76.9%), supporting safety, feasibility, and early signs of efficacy for TAC01-HER2 therapy.
10.1016/j.annonc.2026.05.696
Treatment Effect Reanalysis of the Randomized Individual Screening Trial of Innovative Glioblastoma Therapy in Newly Diagnosed Glioblastoma With External Control Data.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
The study reanalyzed three experimental arms of the phase II INSIGhT trial for newly diagnosed glioblastoma patients (ClinicalTrials.gov identifier: NCT02977780), using internal and external control data to estimate treatment effects. Experimental therapies—abemaciclib (n=72, HR 1.00 [95% CI 0.75–1.34]), neratinib (n=80, HR 0.93 [95% CI 0.70–1.24]), and CC-115 (n=12, HR 0.88 [95% CI 0.41–1.88])—did not demonstrate improved survival compared to internal controls receiving standard chemoradiation (n=70). External controls were constructed through propensity score matching with real-world and clinical trial datasets, and simulations assessed the validity and risks of such trial designs. The authors concluded that while external controls can provide valid estimates similar to internal controls, their reliability depends on the availability of comprehensive data to mitigate unmeasured confounding bias.
10.1200/JCO-25-01586
Association between patient-reported outcomes and pathological response in neoadjuvant chemoimmunotherapy-a post hoc analysis of the TD-FOREKNOW trial.
TRANSL LUNG CANCER R · Q1 JOURNAL - RANK #26/108
This post hoc analysis of the randomized phase 2 TD-FOREKNOW trial examined whether pathologic complete response (pCR) correlates with patient-reported outcomes (PROs) in stage IIIA–IIIB NSCLC treated with neoadjuvant camrelizumab plus chemotherapy or chemotherapy alone followed by surgery. Among 94 randomized patients, PRO analyses focused on 40 who received camrelizumab plus chemotherapy and completed ≥1 PRO assessment (14 pCR; 26 non-pCR), using change-from-baseline comparisons of global health status/quality of life, cough, dyspnea, and hemoptysis. GHS/QoL declined during neoadjuvant therapy and recovered postoperatively in both groups; pCR patients had greater improvements during treatment in cough (LS mean difference −18.2; 95% CI −33.0 to −3.5; P=0.02) and dyspnea (−21.3; 95% CI −38.3 to −4.3; P=0.02) versus non-pCR. The study concludes pCR is associated with superior PROs, suggesting pCR may reflect patient-centered benefits beyond survival.
10.21037/tlcr-2025-1-1425
Long-term outcomes after proton therapy vs. intensity-modulated photon radiotherapy with concurrent chemotherapy for locally advanced non-small-cell lung cancer: post-hoc analysis of a prospective randomized trial.
INT J RADIAT ONCOL · Q1 JOURNAL - RANK #14/212
This prospective randomized trial investigated the long-term effects of passive-scattering proton therapy (PSPT) versus intensity-modulated photon radiotherapy (IMRT) with concurrent chemotherapy for locally advanced non-small-cell lung cancer (NSCLC). Researchers measured toxicity, local failure, and survival, including radiation pneumonitis (10.9% IMRT vs 10.5% PSPT), esophageal toxicity, and major adverse cardiac events (MACE). PSPT led to fewer radiation-related MACEs, likely related to reduced coronary artery doses, while no differences were seen in local failure or progression-free survival. Overall survival was comparable to the RTOG 0617 trial among similar-stage NSCLC patients with good performance status.
10.1016/j.ijrobp.2026.05.012
Debio 0123, a WEE1 kinase inhibitor: Phase 1 results from dose escalation in patients with advanced solid tumors.
EUR J CANCER · Q1 JOURNAL - RANK #45/326
This phase 1 dose escalation clinical trial evaluated the WEE1 kinase inhibitor Debio 0123 in 27 patients with relapsed/refractory advanced solid tumors. The oral daily treatment was assessed for safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity across doses from 30 to 350 mg. Key findings included any-grade treatment-related adverse events in 92.6% of patients, grade 3 events in 33.3% (most commonly QTcF prolongation at 11% and fatigue at 7%), and a maximum tolerated dose of 260 mg once daily. The study concluded that Debio 0123 has a manageable toxicity profile, linear pharmacokinetics, target engagement at ≥200 mg, and supports further investigation in selected indications.
10.1016/j.ejca.2026.116792
Near-infrared fluorescence imaging-guided surgery using cRGD-ZW800 to improve surgical resection margins in oral cancer: a phase I/II feasibility trial.
NAT COMMUN · Q1 JOURNAL - RANK #10/135TOP-TIER
This prospective, single-center phase I/II trial (n=31; NCT04191460) evaluated the safety and feasibility of cRGD-ZW800-1, a near-infrared fluorescent integrin-targeted tracer, in improving surgical resection margins for oral squamous cell carcinoma (OSCC). Patients received 0.01, 0.025, or 0.05 mg/kg cRGD-ZW800-1, with tracer uptake quantified using in vivo spectroscopy to optimize dosing and timing. All doses were well tolerated, achieving tumor-to-background ratios >4.5 (optimal at 0.025 mg/kg), and fluorescence imaging detected all 23 inadequate margins (100% sensitivity vs. 70% conventional), altering surgical plans in five cases and avoiding adjuvant radiotherapy in three. The study concludes that cRGD-ZW800-1 is safe, tumor-specific, and enhances intraoperative margin assessment in OSCC.
10.1038/s41467-026-73554-7
Phase 1/2 study of pegenzileukin, a pegylated recombinant non-alpha IL-2, with cemiplimab for the treatment of advanced unresectable or metastatic skin cancers.
J IMMUNOTHER CANCER · Q1 JOURNAL - RANK #12/183TOP-TIER
This phase 1/2 open-label, multicenter clinical trial evaluated pegenzileukin, a pegylated non-alpha IL-2, in combination with cemiplimab for advanced melanoma (MM) and cutaneous squamous cell carcinoma (CSCC). The primary endpoint was objective response rate (ORR), which reached 40% in MM and 56.3% in CSCC at the recommended phase 2 dose (RP2D), with a duration of response ≥12 months in 75.0% and 85.7% of responders, respectively. Secondary endpoints included progression-free survival (PFS), with rates of 55.0% in MM and 70.7% in CSCC at 6 months. The treatment showed manageable safety, with common adverse events being mild infusion-related reactions and robust NK and CD8 T-cell expansion supporting its mechanism of action (NCT04913220).
10.1136/jitc-2025-014347
Cadonilimab induction and consolidation for unresectable stage III non-small cell lung cancer patients receiving concurrent chemoradiation: safety run-in results of a prospective, phase II trial.
TRANSL LUNG CANCER R · Q1 JOURNAL - RANK #26/108
This prospective, single-arm phase II trial evaluated cadonilimab, a bispecific PD-1/CTLA-4 antibody, given as two cycles of induction with chemotherapy, followed by concurrent chemoradiotherapy and up to 1 year of cadonilimab consolidation in 20 patients with unresectable, driver-mutation-negative stage III NSCLC. Safety was the primary focus of this pre-specified run-in; dose-limiting toxicity (DLT) was defined as ≥grade 3 non-hematologic events lasting >7 days, any grade 4 non-hematologic event, or grade 5 potential treatment-related event within 90 days after cCRT. After a median 8.4 month follow-up, 19/20 completed cCRT and 17/20 began consolidation; 4 patients (20 %) experienced DLTs (pneumonitis 2, colitis 1, grade 5 pneumonia 1), while all patients experienced TRAEs, with grade 3–4 non-hematologic TRAEs in 50 %. The manageable safety profile supports ongoing enrollment to further evaluate efficacy and long-term outcomes of cadonilimab with cCRT in stage III NSCLC.
10.21037/tlcr-2026-1-0122
Bladder Adjuvant Radiotherapy: Phase III Multicenter Randomized Controlled Trial of Adjuvant Radiotherapy or Observation for Postcystectomy Muscle-Invasive Bladder Cancer.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
Objective: assess adjuvant radiotherapy (RT) after chemotherapy and radical cystectomy (RC) in high-risk muscle-invasive bladder cancer (MIBC) in a multicenter, phase III randomized trial. Patients (n=153; pT3–4 62%, pN+ 41%) were randomized 1:1 to stoma-sparing IG-IMRT 50.4 Gy/28 fractions to cystectomy bed/pelvic nodes versus observation, stratified by nodal status and chemotherapy; >90% received perioperative chemotherapy (71% neoadjuvant, 20% adjuvant). After median 47 months, 2-year LRFS was 87.1% vs 76.0% (HR 0.43, 95% CI 0.20–0.96, p=0.04); DFS 71.6% vs 58.7% (HR 0.62, 95% CI 0.36–1.05), BCSS 79.6% vs 65.0% (HR 0.59, 95% CI 0.33–1.10), and OS 70.4% vs 57.4% (HR 0.78, 95% CI 0.49–1.26). The authors conclude adjuvant pelvic IMRT improves locoregional control without added severe toxicity, with nonsignificant trends toward improved DFS/BCSS/OS.
10.1200/JCO-25-02093
Intraperitoneal and Intravenous Paclitaxel Plus S-1 for Gastric Cancer With Peritoneal Metastasis: A Phase 3 Randomized Clinical Trial.
JAMA ONCOL · Q1 JOURNAL - RANK #14/326TOP-TIER
Objective: determine whether adding intraperitoneal paclitaxel to intravenous paclitaxel plus S-1 improves overall survival in gastric cancer with peritoneal metastasis. Methods: DRAGON-01, multicenter open-label phase 3 RCT in 9 Chinese hospitals (2017–2022; cutoff Mar 11, 2025) enrolled adults with peritoneal-only metastatic gastric adenocarcinoma; randomized 2:1 to IP+IV paclitaxel plus S-1 vs IV paclitaxel plus S-1; primary OS; 222 treated. Results: median OS 19.4 vs 13.9 months (HR 0.67, 95% CI 0.50–0.90; P=.01); median PFS 11.2 vs 7.2 months (HR 0.72, 95% CI 0.54–0.96); grade 3–4 AEs 38.5% vs 41.9%; no treatment-related deaths. Conclusion: Intraperitoneal paclitaxel added to standard PS improved survival without increasing severe toxicity in first-line treatment.
10.1001/jamaoncol.2026.1347
Fulvestrant versus capecitabine as maintenance therapy in hormone receptor-positive, HER2-negative metastatic breast cancer after first-line chemotherapy (FAMILY): a multicenter, open-label, randomized, phase 3 trial.
SIGNAL TRANSDUCT TAR · Q1 JOURNAL - RANK #1/319TOP-TIER
This multicenter, open-label, randomized phase 3 trial evaluated fulvestrant versus capecitabine as maintenance therapy in hormone receptor-positive, HER2-negative metastatic breast cancer patients after first-line chemotherapy response or disease control. 210 patients were randomized equally to the two treatment groups, with a median follow-up of 33.6 months. Fulvestrant significantly improved progression-free survival (PFS) compared to capecitabine (17.3 vs. 9.0 months, hazard ratio 0.63, p=0.003), while grade ≥3 adverse events were lower in the fulvestrant group (2.9% vs. 10.5%). The study concludes that fulvestrant offers superior PFS and a favorable safety profile for maintenance therapy in this patient population.
10.1038/s41392-026-02720-6
Biomarker study of pembrolizumab in patients with advanced rare cancers.
CELL REP MED · Q1 JOURNAL - RANK #15/195TOP-TIER
This prospective phase 2 clinical trial evaluated pembrolizumab in 154 patients (142 evaluable) with advanced rare cancers, aiming to identify predictive biomarkers of clinical benefit. Objective response rate was 14.8%, and overall clinical benefit (CB) was 26.8%. CB was strongly associated with MSI-H/TMB-H status (OR: 13.9, p=0.0013) and PD-L1 CPS ≥10 (p=0.0285), though some biomarker-negative tumors also responded; immune profiling revealed that CB tumors had higher baseline T cell infiltration and activation. The study concludes that immune microenvironment features may serve as predictive markers for pembrolizumab efficacy beyond genomic assays, highlighting the role of immune cell recruitment during therapy.
10.1016/j.xcrm.2026.102827
Datopotamab deruxtecan (Dato-DXd) in combination with durvalumab as first-line treatment for unresectable locally advanced or metastatic triple-negative breast cancer: results from arms 7 and 8 of the phase Ib/II BEGONIA study.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
The BEGONIA study is a phase Ib/II, open-label clinical trial assessing the safety and efficacy of datopotamab deruxtecan (Dato-DXd) combined with durvalumab as first-line treatment for unresectable locally advanced or metastatic triple-negative breast cancer (TNBC). Arms 7 and 8 of the study evaluated patients with different PD-L1 tumor expression levels receiving Dato-DXd (6 mg/kg) and durvalumab (1120 mg) every three weeks. In Arm 7 (n=62), the confirmed objective response rate (cORR) was 79.0%, with a median duration of response (DoR) of 17.6 months. In Arm 8 (n=33), the cORR was 81.8%, although DoR and progression-free survival (PFS) data were immature due to shorter follow-up. The combination demonstrated promising antitumor activity with a manageable safety profile.
10.1016/j.annonc.2026.05.693
CRISPR-Cas9 CD33-deleted allogeneic hematopoietic cell transplantation with gemtuzumab ozogamicin maintenance in AML: a phase 1/2 trial.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This multicenter phase 1/2a open-label trial evaluated trem-cel, a CRISPR-Cas9 gene-edited allogeneic hematopoietic cell transplantation (HCT) product lacking CD33, followed by gemtuzumab ozogamicin (GO) maintenance in 30 high-risk AML/MDS patients. The primary endpoint was neutrophil engraftment by day 28, which was achieved in all patients, with a median engraftment time of 10 days (95% CI: 9-10). Nineteen patients received GO maintenance, which was tolerated up to 2 mg/m² without prolonged high-grade cytopenias, though three cases of transplant-related mortality occurred. The trial concluded that trem-cel enabled safe engraftment and GO maintenance without prolonged hematologic toxicity.
10.1038/s41591-026-04362-1
Use of circulating tumour DNA to prospectively guide a switch from targeted to immune therapy in BRAF mutant advanced melanoma: the randomised phase II CAcTUS trial.
NAT COMMUN · Q1 JOURNAL - RANK #10/135TOP-TIER
The randomized, parallel-arm phase II CAcTUS trial prospectively evaluated circulating tumour DNA (ctDNA) to guide transition between targeted therapy (TT) and checkpoint inhibitor immunotherapy (CPI) for BRAF mutant advanced melanoma. Twenty-one patients were randomized to receive TT or CPI, switching treatments based on either progression or achieving ≥80% reduction of BRAF variant allele frequency (VAF) in ctDNA, with 100% critical results obtained within 7 days (95% CI: 94-100%) and 100% TT patients achieving ≥80% reduction (95% CI: 80-100%). Secondary outcomes assessed progression-free and overall survival, with no new safety signals observed. The findings demonstrate ctDNA’s feasibility for timely treatment decisions, optimizing therapy sequencing.
10.1038/s41467-026-72735-8
Randomized Phase II Trial of Consolidation Pembrolizumab After Definitive Chemoradiotherapy in Locally Advanced Nasopharyngeal Carcinoma: KCSG HN19-09, CONPELAN Study.
HEAD NECK-J SCI SPEC · Q1 JOURNAL - RANK #15/67
In this prospective, randomized phase II trial, patients with stage II-IVB nasopharyngeal carcinoma were allocated 2:1 to receive either consolidation pembrolizumab or placebo following definitive chemoradiotherapy. The main objective was to evaluate 3-year progression-free survival (PFS), with additional analyses of toxicity and immune-related biomarkers. Among 53 participants, the 3-year PFS rates were 56.5% for pembrolizumab and 57.8% for placebo (p=0.142, HR=0.408), and grade ≥3 adverse events occurred in 8.8% of the pembrolizumab arm. Although consolidation pembrolizumab did not significantly improve PFS in unselected patients, exploratory analyses revealed a possible beneficial effect in those with high intratumoral TIL density, suggesting further research is warranted.
10.1002/hed.70329
Cardiac Radiation Dose and Subclinical Coronary Artery Disease Progression after Breast Cancer Radiotherapy: 2-year Cardiac CT Results from the EARLY-HEART Study.
RADIOL-CARDIOTHORAC · Q1 JOURNAL - RANK #30/212
This secondary analysis of the prospective multicenter EARLY-HEART study evaluated 224 asymptomatic female breast cancer patients treated with radiation therapy post-lumpectomy, using cardiac CT scans before and 24 months after treatment. The study assessed cardiac radiation dose and progression of coronary artery calcium (CAC), finding that higher cardiac radiation doses were associated with increased CAC progression (whole heart relative risk: 2.0 [95% CI: 1.5, 2.8]; p < .001) at 2-year follow-up, particularly among those with baseline calcification. Coronary stenosis progression, observed in 36 patients, did not correlate with cardiac radiation dose but was linked to higher baseline CACS and CAC progression (p < .001). The authors conclude that cardiac radiation dose is a predictor of subclinical coronary artery disease progression post-breast cancer radiotherapy.
10.1148/ryct.250342
A Multicenter Phase II Study on Atezolizumab plus Bevacizumab Combination Therapy in Patients with Unresectable Hepatocellular Carcinoma and Child-Pugh Classification B Cirrhosis: CHALLENGE Trial.
LIVER CANCER · Q1 JOURNAL - RANK #11/147
This multicenter, open-label, single-arm phase II study assessed the safety and efficacy of atezolizumab (1,200 mg) plus bevacizumab (15 mg/kg) in 30 patients with unresectable hepatocellular carcinoma (HCC) and Child-Pugh B cirrhosis (scores 7-8). The primary endpoint of serious adverse events (SAEs) revealed a frequency of 23.3% (95% CI: 9.9–42.3%; p < 0.0001), while the objective response rates were 40.0% and 46.7% based on RECIST v1.1 and modified RECIST, respectively. Median progression-free survival was 240 days (95% CI: 176–526), and median overall survival was 470 days (95% CI: 256–576). The study concluded that this combination therapy is safe, with demonstrable antitumor activity, and further studies are necessary to confirm its potential in this patient population.
10.1159/000551476
Cluster Randomized Trial of Intensive Systolic Blood Pressure Control in Patients With Renal Cell or Thyroid Cancer Receiving VEGFR Tyrosine Kinase Inhibitors: ECOG-ACRIN EAQ191.
HYPERTENSION · Q1 JOURNAL - RANK #7/98
This cluster randomized controlled trial assessed the feasibility and safety of intensive systolic blood pressure (SBP) control (<120 mmHg) versus usual care (<140 mmHg) in patients with renal cell or thyroid cancer initiating VEGFR tyrosine kinase inhibitors. A phase II site-based design used 10 sites (5 per arm) enrolling 61 patients (58 renal cell, 3 thyroid), with centralized BP advisory core guidance, home monitoring, and visits at baseline, 1, 2, 3, and 6 months. Mean SBP differences favored intensive control: -12.2 mmHg (95% CI -18.1 to -7.0) at 1 month, -7.6 (95% CI -15.3 to -0.4) at 3 months, and -6.9 (95% CI -19.3 to 6.0) at 6 months; grade 3 adverse events were numerically higher in usual care for kidney injury, hypotension, and dyspnea. The authors conclude this first randomized trial in active cancer patients demonstrates feasibility, safety, and tolerability of intensive SBP control.
10.1161/HYPERTENSIONAHA.125.26016
Efficacy and safety of elranatamab in patients with relapsed or refractory multiple myeloma: A US subgroup analysis from MagnetisMM-3.
CANCER-AM CANCER SOC · Q1 JOURNAL - RANK #68/326
Elranatamab was evaluated for efficacy and safety in relapsed or refractory multiple myeloma within a U.S. subgroup from the prospective MagnetisMM-3 trial (NCT04649359). In this post hoc analysis, 47 BCMA-naive patients received 76 mg of elranatamab weekly, followed by less frequent dosing upon durable responses. At a median follow-up of 39.6 months, the objective response rate was 66.0% (95% CI, 50.7-79.1); 42.6% (95% CI, 28.3-57.8) achieved complete response or better, median duration of response was 40.8 months (24.0-not estimable [NE]), progression-free survival was 27.3 months (4.3-NE), and overall survival was 43.6 months (14.9-NE). The results indicate elranatamab’s durable efficacy and acceptable safety in a heavily pretreated population, consistent with the overall MagnetisMM-3 BCMA-naive group.
10.1002/cncr.70442
Cryoablation for early-stage invasive breast cancer: pathologic and imaging outcomes from the prospective FIRST trial.
BREAST CANCER RES · Q1 JOURNAL - RANK #57/326
The prospective, multicenter, single-arm phase II FIRST trial aimed to determine the pathological efficacy and safety of ultrasound-guided cryoablation for early-stage invasive breast cancer, correlate imaging and pathology, and identify technical predictors for successful tumor ablation. Forty-eight patients with unifocal tumors ≤2.5 cm were treated, followed by surgical resection 14-28 days post-cryoablation. The invasive complete ablation rate was 97.9%, 100% for tumors ≤2.0 cm, with high negative predictive value for MRI (93.0%), limited residual ductal carcinoma in situ in 12.5%, and minimal adverse events. Cryoablation showed promise as a safe and effective minimally invasive approach but remains investigational, requiring phase III trials to define its role in breast-conserving strategies.
10.1186/s13058-026-02302-y
Integration of venetoclax into a fludarabine and melphalan conditioning regimen in patients aged 50 years and older with acute myeloid leukemia and myelodysplastic syndrome: Results from a phase 2 clinical trial.
CANCER-AM CANCER SOC · Q1 JOURNAL - RANK #68/326
This phase 2 multicenter clinical trial evaluated a venetoclax, fludarabine, and melphalan (VFM) conditioning regimen for allogeneic hematopoietic stem cell transplantation in 60 patients aged 50–66 years with acute myeloid leukemia or myelodysplastic syndrome. The primary endpoint of 2-year disease-free survival was 75.0% (95% CI, 64.8%–86.8%), with 2-year overall survival of 78.3% (95% CI, 68.6%–89.5%) and relapse rate of 11.7% (95% CI, 5.1%–21.3%). Grade 2–3 nonhematologic adverse events occurred in 58% of patients, with no grade 4–5 toxicities; cumulative incidence of grade 2–4 acute graft-versus-host disease at day 100 was 5.0%. The authors concluded that VFM conditioning is feasible in older adults, with low rates of graft-versus-host disease and relapse supporting further study.
10.1002/cncr.70467
Five-Year Survival with Tebentafusp in Metastatic Uveal Melanoma.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
An international, open-label, randomized phase 3 trial (NCT03070392) evaluated 5-year overall survival with tebentafusp versus investigator’s choice (pembrolizumab, ipilimumab, or dacarbazine) in previously untreated HLA-A*02:01-positive adults with metastatic uveal melanoma, stratified by LDH; exploratory endpoints included ctDNA dynamics. After ≥5 years’ follow-up, median OS was 21.6 months with tebentafusp versus 16.9 months with control (stratified HR 0.67; 95% CI 0.54–0.85), and 5-year OS rates were 16% versus 8%. Benefit extended to poor-prognosis subgroups (e.g., tumors ≥10 cm or RECIST progressive disease), and post hoc analyses suggested longer OS with treatment beyond radiographic progression. Undetectable baseline ctDNA or ≥50% ctDNA reduction by week 9 correlated with longer OS, supporting durable survival benefit of tebentafusp.
10.1016/j.annonc.2026.05.695
A randomized controlled trial comparing robotic NOSES versus robotic TME for Mid-rectal cancer: short-term oncological and perioperative outcomes.
J ROBOT SURG · Q1 JOURNAL - RANK #48/312
The study aimed to compare perioperative and short-term oncological outcomes between robotic NOSES and robotic TME for mid-rectal cancer in a prospective randomized clinical trial involving 150 eligible participants, with 140 analyzed (71 R-TME and 69 R-NOSES). Methodologically, the trial employed 1:1 randomization and measured intraoperative and pathological metrics such as blood loss, operative duration, and lymph node harvest, as well as postoperative recovery indicators. While overall complication rates were similar (R-NOSES 13.0% vs. R-TME 15.5%, P=0.679), R-NOSES had statistically lower wound complications (0.0% vs. 5.6%, P=0.045), earlier flatus and diet resumption, and reduced VAS pain scores. The authors conclude R-NOSES is safe and offers superior recovery benefits compared to R-TME for selected mid-rectal cancer patients.
10.1007/s11701-026-03494-3
Longitudinal transcriptomic profiling identifies predictors of response to neoadjuvant chemoimmunotherapy in triple-negative breast cancer: results from the NeoTRIPaPDL1 trial.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
The NeoTRIPaPDL1 phase III randomized trial enrolled 280 patients with high-risk triple-negative breast cancer, assigning them to neoadjuvant chemotherapy with or without atezolizumab. Longitudinal biopsies were collected for transcriptomic profiling, and associations between gene signatures and pathologic complete response (pCR) were evaluated via logistic regression and XGBoost models. Key findings include higher baseline tumor proliferation and lower stromal/metabolic signatures correlating with increased pCR in the chemoimmunotherapy arm, while early on-treatment immune activation and tumor clearance strongly predicted pCR across both arms. The principal conclusion is that dynamic gene expression changes and early tumor clearance are robust predictors of pCR, supporting adaptive neoadjuvant strategies for TNBC.
10.1016/j.annonc.2026.05.694
Economic evaluation of lymphaticovenous anastomosis versus conservative therapy for breast-cancer related lymphoedema: secondary outcome analysis of a randomized controlled trial.
BJS-BRIT J SURG · Q1 JOURNAL - RANK #5/312
This study is a pre-specified secondary outcome analysis of a randomized controlled trial evaluating the cost-effectiveness of lymphaticovenous anastomosis (LVA) combined with complex decongestive therapy (CDT) versus CDT alone for breast cancer-related lymphoedema. The trial included 100 female patients from four Dutch hospitals and adopted a societal perspective with a 2-year time horizon, deriving Quality-Adjusted Life Years from the EuroQol-5D-5L. Mean total costs were €16,234 (LVA) vs €14,293 (CDT) with an adjusted mean difference of €78, while mean QALYs were 1.636 vs 1.579 with an adjusted difference of 0.045, yielding a societal ICER of €1,716/QALY. The authors conclude that LVA combined with CDT has potential to be cost-effective from a societal perspective, particularly when performed under local anaesthesia.
10.1093/bjs/znag062
Pembrolizumab with or without chemotherapy among older adults with advanced lung adenocarcinoma: a national, nonrandomized open-label phase II trial (Alliance A171901).
JNCI-J NATL CANCER I · Q1 JOURNAL - RANK #44/326
This multicenter, nonrandomized open-label phase II trial (Alliance A171901; NCT04533451) evaluated first-line pembrolizumab with or without carboplatin/pemetrexed in adults aged ≥70 years with stage IV or recurrent lung adenocarcinoma, with the primary endpoint being the 6-month rate of solicited grade ≥3 adverse events and secondary endpoints including overall survival and quality of life. Among 95 evaluable patients (43 monotherapy; 52 combination; median age 77; 11.6% ECOG ≥2), grade ≥3 adverse events within 6 months occurred in 25.6% (95% CI 13.5–41.2) with monotherapy and 42.3% (95% CI 28.7–56.8) with combination therapy. Median overall survival was 16.4 months (95% CI 10.1–not estimable) versus 29.9 months (95% CI 16.4–not estimable), quality of life worsened during treatment, and a geriatric toxicity risk score did not predict severe AEs. The authors conclude AE rates are comparable to prior registration trials and support inclusion of older adults in future trials.
10.1093/jnci/djag157
Exploratory analysis of PTEN deficiency by immunohistochemistry from the Phase III CAPItello-291 trial.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
This study aimed to explore the utility of immunohistochemistry (IHC) for identifying PTEN deficiency in hormone receptor-positive/HER2-negative advanced breast cancer, using samples from the Phase III CAPItello-291 clinical trial. PTEN IHC was performed on 367 tumor samples, with 19.1% classified as PTEN deficient; concordance between IHC and next-generation sequencing (NGS) results was 87.0% overall. Among PTEN-deficient cases, patients receiving capivasertib plus fulvestrant showed improved progression-free survival compared to placebo plus fulvestrant (median 9.3 vs 3.7 months; hazard ratio: 0.52, 95% CI: 0.28-0.90). The principal conclusion is that IHC may help identify patients eligible for capivasertib plus fulvestrant treatment based on PTEN status.
10.1158/1078-0432.CCR-25-2965
Tucidinostat Plus R-CHOP vs R-CHOP in MYC/BCL2 Double-Expressor Diffuse Large B-Cell Lymphoma: A Randomized Clinical Trial.
JAMA-J AM MED ASSOC · Q1 JOURNAL - RANK #4/332TOP-TIER
This double-blind, placebo-controlled phase 3 randomized clinical trial evaluated the efficacy and safety of tucidinostat plus R-CHOP versus R-CHOP alone as a first-line treatment for patients with MYC/BCL2 double-expressor diffuse large B-cell lymphoma (DEL). A total of 423 patients participated, with a median follow-up of 41.3 months. Tucidinostat reduced the risk of disease progression, relapse, death, or need for new therapy by 28% (HR, 0.72 [95% CI, 0.54-0.96]; P = .02) and improved the 2-year event-free survival rate (60.3% vs. 50.5%) and complete response rate (73.0% vs. 61.8%; difference 11.1% [95% CI, 2.3%-20.0%]). The trial demonstrated that tucidinostat plus R-CHOP significantly improves survival outcomes with manageable toxicity, representing a novel first-line treatment for this high-risk patient population.
10.1001/jama.2026.4199
Phase Ib of repotrectinib plus osimertinib in patients with EGFR-mutated advanced non-small cell lung cancer.
LUNG CANCER · Q1 JOURNAL - RANK #19/108
TOTEM (NCT04772235) was a phase Ib, prospective clinical trial evaluating repotrectinib plus osimertinib in EGFR-mutated advanced NSCLC resistant to prior therapies, using 3+3 dose-escalation (osimertinib 80 mg QD plus repotrectinib 80 mg QD, 160 mg QD, or 160 mg BID) followed by dose expansion post-osimertinib or post-osimertinib+chemotherapy. Thirty-one patients were enrolled (Feb 2022–Jan 2025); the recommended phase 2 dose was osimertinib 80 mg QD plus repotrectinib 160 mg BID. Grade 3–4 treatment-related adverse events occurred in 45.2%, most commonly dizziness (16.1%) and anemia (12.9%); ORR was 22.2% (95% CI 8.6–42.3) with six confirmed partial responses and a DoR of 6.9 months (95% CI 2.7–13.1), and median PFS was 4.0 months (95% CI 2.8–9.7). In patients with intracranial disease, icORR was 33.3% (95% CI 7.5–70.1) and median icPFS was 4.4 months (95% CI 2.7–NR), supporting further investigation.
10.1016/j.lungcan.2026.109461
Pembrolizumab combined with nab-paclitaxel and platinum in recurrent/metastatic HNSCC: efficacy, safety, and survival predictive model.
ESMO OPEN · Q1 JOURNAL - RANK #36/326
This single-arm phase 2 study assessed the efficacy and safety of pembrolizumab combined with nab-paclitaxel and platinum for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). At a 23-month median follow-up (95% CI 19.4-29.6), the objective response rate was 64.2%, disease control rate was 93.2%, progression-free survival was 12.7 months (95% CI 10.2-14.7), and overall survival was 21.8 months (95% CI 18.9-35.7). Hypothyroidism (27%, including one grade 3 case) was the most common immune-related adverse event. A seven-parameter clinical predictive model showed strong prognostic accuracy for stratifying patient risk, with AUCs from 0.753 to 0.919 for progression-free survival and 0.682 to 0.908 for overall survival prediction across training and test datasets.
10.1016/j.esmoop.2026.107733
Precision-guided therapy in H3K27-altered diffuse midline glioma.
NAT COMMUN · Q1 JOURNAL - RANK #10/135TOP-TIER
This prospective clinical trial enrolled 68 children with H3K27-altered diffuse midline glioma (DMG) into the PRISM precision medicine study (NCT03336931). A total of 58 (85%) patients underwent whole-genome sequencing and RNAseq, with precision-guided therapy (PGT) recommended for 50 (74%). Eighteen patients receiving PGT were evaluable for survival, showing an overall response rate of 48% and median overall survival of 21.3 months versus 12.1 months for non-PGT recipients (p=0.34). The study concludes that PGT is feasible and may offer clinical benefit, particularly when administered after tumor progression.
10.1038/s41467-026-73304-9
A chemotherapy-free, pathological response-adapted strategy using trastuzumab-pertuzumab and T-DM1 in HER2-positive early breast cancer: the PHERGain-2 study.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This multicenter, single-arm, phase II study evaluated a pCR-guided de-escalation strategy to omit chemotherapy in 396 treatment-naive patients with HER2-positive, node-negative early breast cancer. Patients received neoadjuvant trastuzumab-pertuzumab (HP), with endocrine therapy for hormone receptor-positive tumors, followed by adjuvant HP for pCR (cohort A, 59.6%) or T-DM1 for residual disease (cohort B, 37.8%; cohort C, 1.8%). One-year global HRQoL decline ≥10% occurred in 42.8% overall (37.3% pCR vs. 51.9% residual disease), with 86.6% treatment-related adverse events (5.6% grade ≥3) and one death from pneumonitis. PHERGain-2 demonstrated meaningful HRQoL preservation, expected toxicity, and an outstanding pCR rate comparable to standard chemotherapy plus HP regimens.
10.1016/j.annonc.2026.01.013
TRAM-01: A phase 2 study of trametinib for pediatric patients with neurofibromatosis type 1 and plexiform neurofibromas.
NEURO-ONCOLOGY · Q1 JOURNAL - RANK #4/285TOP-TIER
This phase 2 prospective clinical trial evaluated trametinib in 46 pediatric patients (aged 0.7–19.8 years) with neurofibromatosis type 1 and inoperable plexiform neurofibromas. Trametinib was administered orally daily for up to 18 cycles, with volumetric tumor responses and patient-reported outcomes assessed at multiple intervals. The overall response rate—defined as ≥20% tumor volume decrease—was 47.8% (22/46 patients), and the median volume change was -19.3% (range -80.5 to 3.5); 3-year progression-free and event-free survival rates were 73.1% (95% CI 53.3%-85.5%) and 47.1% (95% CI 28.8-63.5%), respectively. The study concludes trametinib is effective and well tolerated as a treatment for inoperable plexiform neurofibromas in this population.
10.1093/neuonc/noag112
EV-103 dose escalation/cohort A: 5-year follow-up of enfortumab vedotin plus pembrolizumab in previously untreated locally advanced/metastatic urothelial carcinoma.
ESMO OPEN · Q1 JOURNAL - RANK #36/326
This phase Ib/II EV-103/KEYNOTE-869 study evaluated enfortumab vedotin (EV) plus pembrolizumab (P) in cisplatin-ineligible patients with previously untreated locally advanced/metastatic urothelial carcinoma (la/mUC). Forty-five patients received EV 1.25 mg/kg on days 1 and 8 and pembrolizumab 200 mg on day 1 of 3-week cycles, with a primary endpoint of safety and secondary endpoints including ORR, DOR, PFS, and OS. After a median 62.1-month follow-up, the confirmed ORR was 73.3%, median DOR was 22.1 months, median PFS was 12.7 months, median OS was 26.1 months, and the estimated 5-year survival rate was 41.5%. The authors conclude that these results support EV+P as standard of care in this population.
10.1016/j.esmoop.2026.107700
Dose Escalation With Intensity-Modulated Proton Therapy for Patients with High-Risk Meningiomas - Results From a Phase 1 Trial.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
This prospective single-arm phase 1 trial evaluated the safety and efficacy of dose-escalated intensity-modulated proton therapy (IMPT) in 21 patients with high-risk meningiomas (16 grade 2, 5 grade 3). Patients received 66 Gy(RBE) for grade 2 gross disease or 63 Gy(RBE) for grade 3 tumor beds, with primary endpoints assessing acute dose-limiting toxicity (DLT) and secondary endpoints including progression-free survival (PFS) and overall survival (OS). No DLTs occurred, with 3-year PFS and OS rates of 88.2% and 95.0%, respectively, and five late grade 3 toxicities observed in four patients. The study concluded that dose-escalated IMPT demonstrated favorable early safety and efficacy, warranting further phase 2/3 trials.
10.1158/1078-0432.CCR-25-3856
Lipid Nanoparticle-encapsulated mRNA-2752 Encoding Human OX40L, IL-23, and IL-36γ Plus Durvalumab Induces an Immunostimulatory Effect Within the Tumor Microenvironment in Patients with Advanced Solid Tumors.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
This phase 1 study (NCT03739931) evaluated intratumoral mRNA-2752 (encoding OX40L, IL-36γ, and IL-23) as monotherapy (Arm A) or combined with durvalumab (Arm B) in advanced solid tumors, with primary objectives of safety, tolerability, maximum tolerated dose (MTD), and objective response rate (ORR) per RECIST v1.1 in CPI-resistant melanoma. Among 134 patients (Arm A n=19; Arm B n=115), the MTD was not reached and a recommended dose for expansion ≤8 mg was selected; dose-limiting toxicities were two grade 2 cytokine-release syndrome events in Arm B. Treatment-related adverse events were mostly grade 1/2; grade 3 mRNA-2752–related events occurred in 1/19 (5.3%) in Arm A and 29/115 (25.2%) in Arm B, and confirmed ORR in CPI-resistant melanoma (n=28) was 17.9% (95% CI 6.1–36.9%) with disease control rate 42.9% (95% CI 24.5–62.8%). Biomarkers showed increased peripheral cytokines and sustained inflammatory tumor microenvironment responses, supporting antitumor activity and further development.
10.1158/1078-0432.CCR-25-4643
Genomic alterations and dynamic molecular residual disease monitoring predict pathological response to neoadjuvant chemoimmunotherapy in esophageal squamous cell carcinoma.
FRONT IMMUNOL · Q1 JOURNAL - RANK #32/183
This prospective study enrolled 29 patients with stage II-III esophageal squamous cell carcinoma (ESCC) receiving neoadjuvant chemoimmunotherapy (NCIT) with albumin-paclitaxel/carboplatin plus anti-PD-1. Baseline tumor tissues were analyzed via 437-gene targeted sequencing, and serial plasma samples were profiled using a 2365-gene panel for tumor-informed molecular residual disease (MRD) monitoring. Major pathological response (MPR) was significantly associated with baseline TP53 mutations (p=0.014) and higher chromosomal instability score (p=0.032), while absence of MRD and lower ctDNA levels post-NCIT (but not before or during) strongly correlated with MPR. A combined model of baseline TP53 mutation and post-NCIT MRD status achieved superior MPR prediction (AUC=0.954), outperforming either factor alone.
10.3389/fimmu.2026.1681959
Comparative study between PET-CT simulation and CT for head and neck cancer treatment and their potential effect on the thyroid gland: a prospective comparative study.
RADIAT ONCOL · Q1 JOURNAL - RANK #51/212
This prospective comparative analysis evaluated whether PET-CT simulation offers advantages over CT-alone planning in head and neck cancer (HNC) radiotherapy. Two patient groups (PET-CT versus CT) received radiotherapy, and blood samples were collected pre- and post-treatment to measure TSH, FT3, and FT4. Results showed a 71.8% improvement in GTVp delineation accuracy with PET-CT, accompanied by minor TSH declines but significant drops in FT3 and FT4, mainly in stage II/III patients. Researchers concluded that PET-CT integration enhances RT planning while underscoring the necessity for diligent thyroid function monitoring in HNC treatment.
10.1186/s13014-026-02840-x
Phenotypic and Functional Characteristics of CD8+ T cells Predict Clinical Outcome Following TIL Therapy in a Randomized Phase III Trial in Advanced Melanoma.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
This study evaluated the efficacy of tumor-infiltrating lymphocytes (TIL) therapy in a randomized Phase III clinical trial (TIL-NKI/CCIT) for advanced melanoma. The trial compared TIL treatment to ipilimumab in 80 patients with unresectable stage IIIC and IV cutaneous melanoma, focusing on biomarkers of therapeutic response. Key findings showed a strong correlation between the number of infused CD8+TCRαβ+ T cells and progression-free survival (PFS); higher frequencies of these cells were associated with improved PFS at six months (p<0.0001). The authors concluded that CD8+ T cell characteristics, including phenotype, tumor reactivity, and persistence, are critical predictors of clinical outcomes following TIL therapy.
10.1158/1078-0432.CCR-25-4097
Bone-sparing chemoradiotherapy for anal cancer - Results of a phase II trial by the Danish Anal Cancer Group - The DACG II (NCT05385250).
RADIOTHER ONCOL · Q1 JOURNAL - RANK #22/212
This multicenter phase II trial investigated whether bone-sparing chemoradiotherapy could reduce pelvic insufficiency fracture (PIF) rates in patients with localized anal cancer. Patients prospectively received either standard or optimized bone-sparing radiotherapy plans, with toxicity tracked at baseline, during treatment, and at one-year follow-up, using bone-specific MRI as the primary outcome measure. Of 100 enrolled patients, 97% completed radiotherapy and chemotherapy, and the one-year PIF rate was 27.8%, markedly lower than historic rates of 50%. The study concluded bone-sparing radiotherapy significantly reduced PIF rates without affecting other organ toxicity or target coverage.
10.1016/j.radonc.2026.111605
Survival Analysis of the WSG TP-II Trial: Neoadjuvant Trastuzumab and Pertuzumab Plus Endocrine Therapy Versus Chemotherapy in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
The WSG TP-II trial (NCT03272477) was a multicenter, randomized phase II open-label study comparing 12-week neoadjuvant trastuzumab + pertuzumab with endocrine therapy (ET) versus chemotherapy (paclitaxel) in 207 hormone receptor-positive/HER2-positive early breast cancer patients. The primary endpoint showed superior pathologic complete response (pCR) rates in the chemotherapy arm (56.4% vs. 23.7%), with 5-year survival analysis revealing 100% overall survival (ET arm) versus 97.9% (chemotherapy arm) and invasive disease-free survival rates of 97.7% versus 79.8%. The study demonstrated excellent survival outcomes for both de-escalated chemotherapy and ET approaches with dual HER2 blockade. WSG TP-II confirms the safety and efficacy of pCR-guided adjuvant therapy in this patient population.
10.1200/JCO-25-01047
Durvalumab plus HAIC-FOLFOX followed by maintenance durvalumab for hepatocellular carcinoma with major portal invasion: phase 2 DurHope study.
NAT COMMUN · Q1 JOURNAL - RANK #10/135TOP-TIER
The DurHope study was a single-arm phase 2 clinical trial evaluating durvalumab plus HAIC-FOLFOX as first-line treatment in 30 hepatocellular carcinoma (HCC) patients with Vp3/4 portal vein tumor thrombus (PVTT). Primary endpoint was 1-year overall survival (OS) rate, which was 63.3%, with a median OS of 13.9 months (95% CI, 10.7-NR). Secondary endpoints included progression-free survival, objective response rate, and safety, with exploratory biomolecular analyses revealing immune and chemotherapy resistance signatures. The study concluded that the combination therapy showed promising efficacy and tolerable toxicity, with potential biomarkers for response.
10.1038/s41467-026-73131-y
Long-Term Outcomes of Reduced-Dose Radiotherapy in Patients with Epstein-Barr Virus DNA-Selected Stage III Nasopharyngeal Carcinoma: A 5-Year Follow-Up Secondary Analysis of a Phase II Trial.
INT J RADIAT ONCOL · Q1 JOURNAL - RANK #14/212
This secondary analysis of a single-arm phase II trial evaluated long-term outcomes of reduced-dose radiotherapy in low-risk stage III nasopharyngeal carcinoma (NPC) sensitive to induction chemotherapy (IC). All 215 patients received two cycles of IC; 116 with complete/partial response and undetectable EBV DNA received 60 Gy intensity-modulated radiotherapy (IMRT), while 99 received standard 70 Gy. At 68.1 months median follow-up, 5-year progression-free survival was 90.5% (60 Gy) vs. 79.8% (70 Gy), and overall survival was 96.6% vs. 94.9%; no grade 3-4 late toxicity occurred in the 60 Gy group versus 10.1% in the 70 Gy group. The authors conclude that reduced-dose IMRT achieves favorable survival with limited late toxicities in this selected population.
10.1016/j.ijrobp.2026.05.008
Clinical outcomes and spatial transcriptomic profiles of CD19/20 CAR-T therapy in relapsed or refractory B-cell non-Hodgkin’s lymphoma.
J IMMUNOTHER CANCER · Q1 JOURNAL - RANK #12/183TOP-TIER
This expanded phase I/II prospective clinical trial evaluated the efficacy and safety of bispecific CD19/20 CAR-T cell therapy in 32 patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma (B-NHL), following lymphodepletion. Efficacy endpoints included an overall response rate of 74% (58% complete remission among 31 evaluable patients), with median progression-free and overall survival of 6.8 and 22.1 months, respectively. Adverse events were manageable, with cytokine release syndrome in 53% (12% grade ≥3) and neurotoxicity in 9% (all grade 3, no sequelae). Spatial single-cell transcriptomics of tumor biopsies identified distinct microenvironmental phenotypes correlating with responsiveness, informing mechanisms underlying differential outcomes.
10.1136/jitc-2026-015114
Influence of FLAIR inclusion on patterns-of-failure and outcomes in glioblastoma: results from the UNITED prospective adaptive radiotherapy trial.
RADIOTHER ONCOL · Q1 JOURNAL - RANK #22/212
This post hoc analysis of a prospective phase 2 MR-guided adaptive radiotherapy trial (UNITED; NCT04726397) in newly diagnosed glioblastoma assessed whether including peritumoral FLAIR-hyperintense regions (FHR) in the clinical target volume affects patterns of failure and survival during standard chemo-radiotherapy. Patients underwent weekly online-adaptive MR-Linac planning with GTV as resection cavity plus enhancing tumor, CTV as GTV+5 mm, and optional inclusion of FHR beyond 5 mm, forming three groups: no FHR beyond 5 mm (n=24), FHR present not included (n=27), and FHR included (n=47). Recurrences were predominantly central (65–72%, p=0.717), median recurrent GTV coverage within CTV was 97.9% (p=0.105), and no significant differences in PFS (10.5/8.0/8.6 months, p=0.279) or OS (16.9/15.8/13.4 months, p=0.389) were observed. The study concludes FHR omission within a small-margin MR-guided paradigm does not adversely affect failure patterns or survival.
10.1016/j.radonc.2026.111579
Does Radiation Boost Dose Affect Organ Preservation Rates? A Secondary Analysis of the Organ Preservation in Patients With Rectal Adenocarcinoma Trial.
INT J RADIAT ONCOL · Q1 JOURNAL - RANK #14/212
The prospective, randomized clinical trial in rectal adenocarcinoma tested whether increasing the total radiation boost dose during total neoadjuvant therapy could enhance organ preservation (OP). Patients with stage II/III rectal cancer were enrolled and randomized to different sequences of chemotherapy and chemoradiation, receiving either a standard boost dose (median total 5000 cGy) or a high boost dose (median total 5400 cGy). The unplanned secondary analysis showed no significant difference in clinical complete response or long-term OP rates, with 3-year OP of 52% in the standard-dose group versus 47% in the higher-dose group (P > .05). Investigators concluded that higher-dose boost did not increase the probability or durability of OP.
10.1016/j.ijrobp.2026.03.056
Twenty-year results of the randomized European Organization for Research and Treatment of Cancer trial 22922/10925 evaluating internal mammary chain and medial supraclavicular lymph node irradiation in stage I-III breast cancer.
CA-CANCER J CLIN · Q1 JOURNAL - RANK #1/326TOP-TIER
Randomized EORTC 22922/10925 tested whether internal mammary and medial supraclavicular nodal irradiation (IM-MS-RT) improves outcomes in stage I–III breast cancer with axillary involvement and/or central/medial tumors, assigning 4004 patients (1996–2004) to IM-MS-RT or no IM-MS-RT; median follow-up 22.2 years. At 20 years, overall survival was 61.8% (control) vs 61.0% (IM-MS-RT; HR 1.00, p=.967), disease-free survival 49.0% vs 48.2% (HR 0.97, p=.515), and distant metastases-free survival 59.8% vs 58.9% (HR 0.97, p=.578). Breast cancer mortality was reduced (22.4% vs 18.6%; HR 0.82, p=.006), but deaths not from breast cancer/unknown were higher (15.8% vs 20.4%; HR 1.26, p=.002); toxicities increased with IM-MS-RT (lung fibrosis 6.3% vs 3.2%, cardiac fibrosis 2.7% vs 1.7%, cardiac diseases 15.2% vs 11.7%; severe cardiac 1.9% vs 1.7%, severe lung 0.3% vs 0.0%). IM-MS-RT lowered breast cancer mortality but conferred no long-term overall survival benefit, emphasizing the need for very long-term follow-up.
10.3322/caac.70082
Definitive, stereotactic ablative radiotherapy and endocrine therapy without surgery for select low-risk breast cancers: A prospective, phase II trial.
RADIOTHER ONCOL · Q1 JOURNAL - RANK #22/212
This prospective phase II trial (NCT02945579) tested stereotactic ablative radiotherapy (SABR) plus endocrine therapy (ET) as non-operative treatment for HR+, HER2– cT1N0M0 breast cancer, using 3 months of ET, SABR in five fractions, and vacuum-assisted core biopsy at 6–12 months; co-primary endpoints were pathologic complete response (pCR) and 3-year progression-free survival (PFS). Twenty patients (median age 70.5) were enrolled; 19 were biopsied, with pCR in 10/19 (53%, 95% CI 30–73%) and near-complete response in 7 (37%). Twelve patients omitted surgery and, with median follow-up 44.9 months, had 3-year PFS 92% (95% CI 54–99%), one non–breast cancer death, and no breast cancer recurrences; patient-reported decisional regret and breast-specific outcomes remained stable. The authors conclude SABR plus ET achieves substantial pCR and encouraging tumor control, supporting further evaluation of surgery omission in carefully selected patients.
10.1016/j.radonc.2026.111573
Long-term outcomes of stereotactic ablative body radiotherapy for primary kidney cancer (TROG 15.03 FASTRACK II): a multicentre, non-randomised, phase 2 study.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This study is a non-randomized, phase 2 clinical trial that evaluated long-term outcomes of stereotactic ablative body radiotherapy (SABR) in treating primary renal cell carcinoma in non-surgical patients. Conducted across eight hospitals, the trial enrolled 71 patients, with 70 receiving treatment. After a median follow-up of 62 months, local control was 100% with no recurrences, grade 4 events, or treatment-related deaths reported. Seven (10%) patients experienced grade 3 adverse events within 9 months after treatment, and the study concluded that SABR is a safe and effective non-invasive treatment option for medically inoperable patients with renal cell carcinoma.
10.1016/S1470-2045(26)00091-4
Modern Molecular Profiling Recontextualizes the NRG/RTOG 0539 Trial and Reveals Hidden High-Risk and Radiotherapy Resistant Meningiomas.
NEURO-ONCOLOGY · Q1 JOURNAL - RANK #4/285TOP-TIER
This study reanalyzes data from the NRG/RTOG-0539, the first prospective phase 2 trial stratifying meningioma patients for adjuvant radiotherapy (RT) based on clinical risk, using modern molecular techniques. Tumor samples from 100 patients underwent multi-omic profiling, revealing that 10% of tumors would be reclassified and 7% would be reassigned based on updated WHO grading criteria. The study identified genomic and transcriptomic differences between RT responders and non-responders, indicating molecular predictors such as the Proliferative Molecular Group, CDKN2A/B deletion, and 1p/1q alterations outperformed traditional grading systems in predicting recurrence. These findings suggest molecular biomarkers should be integrated with modern grading frameworks to improve risk stratification and personalize treatment for meningioma patients.
10.1093/neuonc/noag081
Ultra-hypofractionated stereotactic ablative body radiotherapy for primary renal cell carcinoma: 5-year outcomes from a pooled analysis of the FASTRACK trials.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This pooled analysis combined data from two prospective clinical trials (FASTRACK phase 1 and FASTRACK II phase 2) evaluating ultra-hypofractionated stereotactic ablative body radiotherapy (SABR) for medically inoperable or high-surgical-risk primary renal cell carcinoma. 103 treated patients (median age 76.9 years) received either 26 Gy in one fraction for tumors ≤4–5 cm or 42 Gy in three fractions for larger lesions; local control, measured with RECIST v1.1, was the primary endpoint and adverse events were graded with CTCAE. Local control was 100 % at 1 year, 98 % (95 % CI 89-100) at both 3 and 5 years, with only one local failure, while grade ≥3 toxicity occurred in 8 % of patients and no grade 4 events or treatment-related deaths were reported. The authors conclude that SABR achieves durable tumor control with low severe toxicity, warranting randomized comparison with surgery.
10.1016/S1470-2045(26)00170-1