Gastric and Esophageal Cancer
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Jun 01 – Jun 08, 2026
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, randomized phase 2 study evaluated the efficacy of adding ONO-4578, an EP4 antagonist, to nivolumab and chemotherapy as first-line treatment for 226 patients with HER2-negative advanced gastric or gastroesophageal junction cancer. The ONO-4578 group demonstrated a significant improvement in progression-free survival (HR 0.67; p=0.040) and a higher objective response rate of 62.0% compared to 48.7% in the placebo group. Exploratory analyses indicated that clinical benefits were most pronounced in patients with PD-L1 CPS ≥1, while safety profiles remained manageable despite increased rates of diarrhea and anemia. These results suggest that targeting the PGE2-EP4 axis may overcome tumor immunosuppression, providing a promising therapeutic strategy that warrants further validation in phase 3 clinical trials.
10.1200/JCO-26-01072
Cost-Effectiveness of Fecal Immunochemical Testing Alone vs Co-Testing With Helicobacter pylori Stool Antigen.
JAMA-J AM MED ASSOC · Q1 JOURNAL - RANK #4/332TOP-TIER
This Markov model cost-effectiveness analysis, based on a Taiwanese pragmatic trial, evaluated adding one-time Helicobacter pylori stool antigen testing to biennial FIT screening for colorectal cancer. Compared to FIT alone, co-testing was dominant (cost-saving) in Taiwan, with an incremental cost-effectiveness ratio of -$2,094 per QALY gained and a 5-fold return on investment. Co-testing remained cost-effective in US settings when H pylori prevalence exceeded 21.9%, preventing gastric and colorectal cancer mortality. For a clinician focused on cancer, this provides strong evidence that combined screening improves cancer outcomes and is economically favorable, particularly in populations with moderate H pylori prevalence.
10.1001/jama.2026.6908
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 phase 3 randomized trial evaluated the efficacy of perioperative serplulimab combined with neoadjuvant SOX chemotherapy followed by adjuvant serplulimab versus chemotherapy alone in 588 patients with PD-L1-positive resectable gastric or gastro-oesophageal junction adenocarcinoma. In the PD-L1 CPS ≥10 population, median event-free survival was significantly longer with serplulimab (not reached vs 42.0 months; HR 0.65; p=0.0082), a benefit also observed in the intention-to-treat population (HR 0.73; p=0.015). The serplulimab regimen demonstrated a superior safety profile, with grade 3 or worse treatment-related adverse events occurring in 47% of patients compared to 59% in the chemotherapy-only group. These results support perioperative serplulimab as a potent treatment strategy for PD-L1-positive gastric cancer, though long-term overall survival data are still required to confirm definitive clinical advantage.
10.1016/S0140-6736(26)00974-8
Savolitinib in MET-amplified gastric or gastroesophageal junction adenocarcinoma: a phase 2 trial.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This phase 2 multicenter trial evaluated the efficacy and safety of savolitinib, an oral MET inhibitor, in 110 patients with MET-amplified, locally advanced or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma who had progressed on prior systemic therapies. In the pivotal phase cohort of 65 patients, the independent review committee-assessed objective response rate was 32.3% (95% CI: 21.2–45.1%), successfully meeting the predefined efficacy threshold. Regarding safety, grade 3 or higher treatment-related adverse events occurred in 34.5% of the total cohort, with one treatment-related death reported. These results demonstrate that savolitinib provides encouraging antitumor activity and a manageable safety profile for heavily pretreated patients with MET-amplified G/GEJ cancer, warranting further validation in randomized controlled trials.
10.1038/s41591-026-04459-7
May 25 – Jun 01, 2026
Cancer Diagnostic Delay Rates Associated With a Population-Based Screening Trial Evaluating a Cell-Free DNA Multicancer Early Detection Test.
JAMA-J AM MED ASSOC · Q1 JOURNAL - RANK #4/332TOP-TIER
This cross-sectional study used a difference-in-differences design to evaluate whether regional participation in the NHS-Galleri multicancer early detection (MCED) trial affected cancer diagnostic delay rates across 21 regions in England. In the first six months, participating regions saw diagnostic delay rates rise from 28.6% to 29.6%, while non-participating regions decreased from 28.9% to 26.3%, representing a 3.4 percentage point adjusted difference (P < .001). The study highlights that large-scale cancer screening trials can increase system-level demand, evidenced by a 4.8 percentage point increase in delays during the second six-month period and higher referral rates. Clinicians and health systems must account for these “spillover effects” on existing cancer diagnostic pathways when implementing population-based screening interventions to ensure timely care for all suspected cancer patients.
10.1001/jama.2026.6803
Zanidatamab with and without Tislelizumab in HER2-Positive Gastroesophageal Cancer.
NEW ENGL J MED · Q1 JOURNAL - RANK #2/332TOP-TIER
This phase 3 trial compared zanidatamab plus chemotherapy, with or without tislelizumab, against trastuzumab plus chemotherapy as first-line treatment for HER2-positive advanced gastroesophageal adenocarcinoma. At 25.9 months median follow-up, zanidatamab-tislelizumab-chemotherapy and zanidatamab-chemotherapy significantly improved progression-free survival (median 12.4 months for both) versus trastuzumab-chemotherapy (8.1 months) (HR 0.63 and 0.65, P<0.001). Overall survival was also longer with zanidatamab-tislelizumab-chemotherapy (26.4 months) compared to trastuzumab-chemotherapy (19.2 months) (HR 0.72, P=0.004). These results indicate that zanidatamab-based regimens, especially with tislelizumab, offer superior efficacy for this specific cancer, potentially establishing new first-line treatment standards.
10.1056/NEJMoa2517729
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 clinical trial evaluated the safety and preliminary efficacy of TAC01-HER2, an autologous T cell therapy targeting HER2, in 23 patients with advanced or metastatic HER2-positive solid tumors. The study found TAC01-HER2 to be safe and well-tolerated, with cytokine release syndrome being the most common adverse event (60.9%), and no treatment-related deaths. Early efficacy signals included partial responses in 2 of 9 gastric/GEJ cancer patients and a 61.1% disease control rate, with a 6-month overall survival rate of 57.9%. These results suggest TAC01-HER2 is a promising, manageable cellular therapy for heavily pre-treated HER2-positive gastric, GEJ, or esophageal adenocarcinomas, warranting further investigation.
10.1016/j.annonc.2026.05.696
May 18 – May 25, 2026
Preclinical characterization and phase 1 results of TQB2102, a first-in-class HER2 biparatopic antibody-drug conjugate, in patients with advanced solid tumors.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This phase 1, first-in-human trial evaluated the safety, efficacy, and pharmacokinetics of TQB2102, a novel HER2 biparatopic ADC, in 195 patients with advanced solid tumors, primarily metastatic breast, colorectal, and gastric/GEJ cancers. The study found a manageable safety profile with no DLTs and MTD not reached, establishing 6.0 and 7.5 mg/kg as RP2D. Preliminary antitumor activity was observed, with objective response rates of 52.4% in MBC, 38.7% in CRC, and 40.0% in G/GEJ adenocarcinoma, including 47.2% in HER2-low MBC. These findings suggest TQB2102 is a promising therapeutic agent for advanced HER2-expressing solid tumors, warranting further investigation in a phase 3 trial for HER2-low MBC.
10.1016/j.annonc.2026.05.003
May 11 – May 18, 2026
Transforming perioperative treatment of gastro-oesophageal adenocarcinoma: triumphs, setbacks and future horizons.
NAT REV CLIN ONCOL · Q1 JOURNAL - RANK #2/326TOP-TIER
This review consolidates developments in gastro-oesophageal adenocarcinoma (GEA) management, aiming to provide clinicians with a comprehensive guide to state-of-the-art perioperative strategies by synthesizing insights from recent clinical trials. It highlights substantial transformations in GEA treatment, driven by evolving epidemiology and the integration of new therapeutic strategies, including chemotherapy, radiotherapy, immune checkpoint inhibitors, and targeted therapies. The review directly addresses cancer by focusing on GEA, offering crucial updates on its perioperative treatment, encompassing established and investigational approaches like organ preservation and ctDNA-based stratification. This provides clinicians with a structured understanding of current GEA management, emphasizing clinical implications and future directions, thereby enhancing evidence-based practice in oncology.
10.1038/s41571-026-01156-9
May 04 – May 11, 2026
Perioperative Toripalimab Plus Chemotherapy Versus Chemotherapy Alone in Locally Advanced Gastric or Gastroesophageal Junction Cancer: 3-Year Follow-Up of NEOSUMMIT-01 Trial.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
The NEOSUMMIT-01 trial’s 3-year follow-up evaluated perioperative toripalimab plus chemotherapy versus chemotherapy alone in 108 patients with locally advanced gastric or gastroesophageal junction cancer. At 43.2 months median follow-up, the combination significantly improved 3-year event-free survival (74.7% vs 56.2%; HR 0.51, p=.044) and 3-year overall survival (81.3% vs 72.2%; HR 0.45, p=.036). These findings offer a promising new treatment option, directly relevant to cancer management. The study suggests perioperative toripalimab plus chemotherapy could improve survival outcomes for this specific cancer population.
10.1200/JCO-25-02842
Apr 27 – May 04, 2026
Barrett’s Esophagus.
NEW ENGL J MED · Q1 JOURNAL - RANK #2/332TOP-TIER
This review outlines the pathophysiology, diagnostic criteria, and management strategies for Barrett’s esophagus, a condition resulting from chronic reflux that significantly increases the risk of esophageal adenocarcinoma. Diagnosis requires endoscopic identification of a columnar-cell-lined segment ≥1 cm with intestinal metaplasia, while surveillance aims to detect high-grade dysplasia and early-stage malignancy. The study emphasizes early detection to enable curative endoscopic interventions, thereby avoiding the morbidity associated with esophagectomy or systemic chemotherapy. Clinicians should prioritize rigorous surveillance and clinical trial participation to improve risk stratification and outcomes for patients at high risk of progression to cancer.
10.1056/NEJMcp2506887
Apr 13 – Apr 20, 2026
Integrated epidemiological and molecular data inform the relationship between precancer and cancer states of esophageal adenocarcinoma.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This study utilized a prospective cohort of 3,100 patients with esophageal adenocarcinoma (EAC) to investigate the evolutionary relationship between Barrett’s esophagus (BE) and cancer using integrated epidemiological, genomic, and spatial transcriptomic data. Genomic features associated with BE were identified in both BE-positive and BE-negative EAC cases, with advanced tumor stage being the primary variable associated with the absence of visible BE at the time of diagnosis. The research demonstrates that even in cases where BE is not clinically apparent, molecular and phylogenetic evidence suggests a shared evolutionary trajectory, indicating that BE is likely a universal precursor to EAC. These findings support a single-pathway model for EAC development, emphasizing the importance of early detection and refined screening strategies for patients at risk of esophageal cancer.
10.1038/s41591-026-04331-8
Apr 06 – Apr 13, 2026
Tislelizumab Combined With Induction Chemotherapy and Concurrent Chemoradiotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma: A Multicenter, Randomized, Phase II Trial (EC-CRT-002).
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This multicenter, randomized phase II trial evaluated adding the PD-1 inhibitor tislelizumab to induction chemotherapy and concurrent chemoradiotherapy (CRT) for unresectable locally advanced esophageal squamous cell carcinoma, comparing a regimen with 12 cycles of maintenance immunotherapy (Group A) to one without maintenance (Group B). After median follow-up of 22.7 months, Group B (no maintenance) demonstrated significantly better progression-free survival versus historical controls (1-year PFS: 71.9% vs 56.4%; HR 0.54) and improved overall survival (HR 0.42), while Group A showed no PFS benefit (1-year: 52.6%; HR 1.06). The findings are directly relevant to clinicians managing locally advanced ESCC, suggesting that tislelizumab combined with induction chemo and concurrent CRT—but without extended maintenance immunotherapy—provides superior efficacy with manageable toxicity (grade ≥3 AEs: 80.7% in Group B). This challenges the assumption that longer maintenance immunotherapy is necessary and identifies specific biomarkers (PD-L1, CD8+ T-cells, NRF2 mutations, ctDNA) associated with treatment response.
10.1200/JCO-25-03044
Nine-Valent Human Papillomavirus Vaccination and Related Cancers in Males.
JAMA ONCOL · Q1 JOURNAL - RANK #14/326TOP-TIER
This multicenter retrospective cohort study evaluated the effectiveness of the 9-valent HPV vaccine in preventing HPV-related cancers in males aged 9-26 years, finding vaccinated males had a 46% lower risk of developing composite HPV-related cancers (HR 0.54, 95% CI 0.37-0.81) compared to unvaccinated males over up to 10 years of follow-up. The study’s primary focus was on cancer prevention, specifically head and neck, esophageal, anal, and penile cancers, with significant risk reduction maintained across age subgroups (9-14 years: HR 0.58; 15-26 years: HR 0.50). These results directly address cancer prevention as a primary research focus by demonstrating vaccine effectiveness against multiple cancer types. The findings strongly support implementing sex-neutral HPV vaccination policies to reduce the future burden of HPV-associated cancers in males.
10.1001/jamaoncol.2026.0496
Mar 16 – Mar 23, 2026
First-line zolbetuximab plus mFOLFOX6 and nivolumab in unresectable CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: a phase 2 trial.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This phase 2 trial evaluated the efficacy and safety of first-line zolbetuximab combined with mFOLFOX6 and nivolumab in 77 patients with CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma. Results showed a median progression-free survival of 14.8 months overall, which increased to 18.0 months in patients with high CLDN18.2 expression. The objective response rate reached 68.1% in the CLDN18.2-high subgroup, though common adverse events included nausea (80.5%) and decreased appetite (72.7%). These findings suggest that combining CLDN18.2 targeting with chemoimmunotherapy is a viable strategy for advanced gastric cancers, warranting the ongoing phase 3 LUCERNA validation.
10.1038/s41591-026-04306-9
Mar 09 – Mar 16, 2026
Camrelizumab plus CAPOX with camrelizumab based maintenance versus CAPOX alone as initial treatment for gastric or gastro-oesophageal junction adenocarcinoma: randomised phase 3 trial.
BMJ-BRIT MED J · Q1 JOURNAL - RANK #5/332TOP-TIER
This randomized phase 3 trial evaluated the efficacy of adding camrelizumab to CAPOX chemotherapy, followed by camrelizumab-based maintenance, as a first-line treatment for 885 patients with HER2-negative, advanced gastric or gastro-oesophageal junction adenocarcinoma. Results demonstrated significantly improved overall survival in the overall population (median 13.5 vs. 12.1 months; HR 0.80) and the PD-L1 positive population (median 15.0 vs. 12.5 months; HR 0.80) compared to CAPOX alone. The study directly addresses the clinician’s interest in oncology by providing high-level evidence for immunotherapy integration in gastrointestinal cancer management. While camrelizumab plus CAPOX improves survival, the addition of apatinib to maintenance therapy increased toxicity (67.9% grade ≥3 adverse events) without further survival benefit, suggesting camrelizumab plus CAPOX followed by camrelizumab maintenance as the preferred clinical approach.
10.1136/bmj-2025-086115
Advances in the management of metastatic gastric cancer: current strategies and emerging therapeutics.
NAT REV CLIN ONCOL · Q1 JOURNAL - RANK #2/326TOP-TIER
This review article summarizes the evolving treatment landscape for metastatic gastric cancer, focusing on biomarker-informed strategies that integrate immune checkpoint inhibitors and targeted therapies for molecularly defined subgroups. Key findings highlight that standard first-line treatment remains fluoropyrimidine-platinum chemotherapy, with biomarker-driven agents (e.g., for MSI, PD-L1, HER2, claudin 18.2) layered on to improve efficacy, though durable responses are uncommon and most patients experience progression. The review is highly relevant to a clinician interested in cancer as it provides a comprehensive update on current standards and emerging therapeutics, including antibody-drug conjugates and cellular therapies, for a major global malignancy. Primary implications include the necessity of molecular profiling to guide treatment selection and the potential of novel modalities to improve outcomes in this challenging disease.
10.1038/s41571-026-01134-1
Romiplostim versus Placebo for Chemotherapy-Induced Thrombocytopenia.
NEW ENGL J MED · Q1 JOURNAL - RANK #2/332TOP-TIER
This phase 3, international, double-blind, randomized, placebo-controlled trial evaluated romiplostim for persistent chemotherapy-induced thrombocytopenia (CIT) in patients receiving oxaliplatin-based chemotherapy for gastrointestinal cancers. Romiplostim significantly reduced CIT-induced chemotherapy dose modifications, with 84% (92 of 109 patients) in the romiplostim group experiencing no modifications compared to 36% (20 of 56 patients) in the placebo group (odds ratio 10.16; P<0.001). This finding is highly relevant to cancer care as it enables patients with gastrointestinal cancers to maintain optimal chemotherapy dose intensity, which is crucial for treatment efficacy. Romiplostim offers a promising strategy to manage CIT, potentially improving the delivery and outcomes of chemotherapy for patients with gastrointestinal malignancies.
10.1056/NEJMoa2511882
Mar 02 – Mar 09, 2026
Trastuzumab Rezetecan in Human Epidermal Growth Factor Receptor 2-Expressing Advanced Gastric Cancer or Gastroesophageal Junction Adenocarcinoma and Colorectal Cancer: A Multicenter, Open-Label, Phase I Trial.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This multicenter, open-label, phase I trial evaluated the safety and efficacy of trastuzumab rezetecan, a novel HER2-targeted antibody-drug conjugate, in 100 patients with advanced HER2-expressing gastric, gastroesophageal junction (GC/GEJ), or colorectal cancer (CRC). Results showed an objective response rate (ORR) of 45.0% and median overall survival (OS) of 16.3 months in HER2-positive GC/GEJ, while HER2-positive CRC patients achieved an ORR of 40.5% and a median OS of 22.7 months. The study demonstrates that trastuzumab rezetecan provides a viable therapeutic option for heavily pre-treated patients with HER2-expressing gastrointestinal malignancies, showing manageable toxicity with only 5% of patients discontinuing due to adverse events. These findings support the further clinical development of trastuzumab rezetecan as a potent treatment strategy for HER2-expressing solid tumors that have progressed on standard therapies.
10.1200/JCO-25-00716