Non-Small Cell Lung Cancer
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Jun 01 – Jun 08, 2026
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 randomized phase 3 study investigated if adjuvant nivolumab improved disease-free survival (DFS) and overall survival in 935 patients with resected non-small cell lung cancer (NSCLC) without EGFR/ALK alterations, comparing nivolumab to observation after standard adjuvant therapy. After a median follow-up of 72.6 months, median DFS was 71.3 months with nivolumab versus 68.8 months with observation (HR 0.97; P=.39), showing no significant improvement. In patients with PD-L1 ≥50%, median DFS was 89.8 months with nivolumab versus 78.5 months with observation (HR 0.86; P=.22), also without significant benefit. The study concludes that adjuvant nivolumab, in this specific post-adjuvant chemotherapy/radiotherapy setting, does not improve DFS in resected NSCLC, guiding against its use in this context.
10.1001/jama.2026.8992
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
This 7-year update of the phase 3 CROWN study evaluated lorlatinib versus crizotinib as first-line treatment for 296 treatment-naive patients with advanced ALK-positive NSCLC. Lorlatinib demonstrated unprecedented long-term benefit, with median PFS not reached (NR) versus 9.1 months for crizotinib (HR, 0.19), and a 7-year PFS of 55% versus 3%. No new intracranial progression events occurred after 30 months on lorlatinib. These findings are highly relevant for cancer clinicians, indicating that lorlatinib provides superior, durable disease control, potentially transforming advanced ALK-positive NSCLC into a chronic condition.
10.1016/j.annonc.2026.05.692
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
This phase 3 randomized trial (HARMONi-6) compared ivonescimab, a PD-1/VEGF bispecific antibody, plus chemotherapy against tislelizumab plus chemotherapy as first-line treatment for 532 patients with advanced squamous non-small-cell lung cancer. At a median follow-up of 21.4 months, ivonescimab significantly improved median overall survival to 27.9 months compared to 23.7 months with tislelizumab (HR 0.66; p=0.0017). While grade 3 or higher treatment-related adverse events were more frequent in the ivonescimab group (69% vs 59%), the survival benefit remained consistent across key patient subgroups. These results establish ivonescimab plus chemotherapy as a superior first-line therapeutic option, offering a clinically meaningful survival advantage for patients with advanced squamous lung cancer.
10.1016/S0140-6736(26)00966-9
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
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
This phase 3 randomized trial (OptiTROP-Lung05) evaluated the efficacy of sacituzumab tirumotecan plus pembrolizumab versus pembrolizumab monotherapy as first-line treatment for 413 patients with PD-L1-positive advanced non-small-cell lung cancer. The combination therapy significantly improved median progression-free survival compared to pembrolizumab alone (not reached vs. 5.7 months; HR 0.35, p<0.0001), with consistent benefits across PD-L1 expression subgroups. While grade 3 or higher adverse events were more frequent in the combination group (55% vs. 31%), the substantial survival benefit suggests a potential new standard of care for advanced NSCLC. This study directly addresses the clinician’s interest in cancer research by providing high-level evidence for a novel therapeutic strategy in a major malignancy.
10.1016/S0140-6736(26)00968-2
Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, 2026.3.1.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This ASCO Living Guideline provides evidence-based recommendations for targeted therapy in Stage IV non-small cell lung cancer (NSCLC) with driver alterations. It focuses on molecular subtypes such as EGFR, ALK, ROS1, BRAF, and others, offering treatment algorithms. Clinical outcomes include improved progression-free survival and overall survival with matched targeted agents compared to chemotherapy. The guideline directly supports clinical decision-making for advanced NSCLC, aligning with the clinician’s interest in cancer-focused research.
10.1200/JCO-26-00843
Therapy for Stage IV Non-Small Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, 2026.3.1.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This ASCO living guideline provides evidence-based recommendations for the systemic treatment of patients with Stage IV non-small cell lung cancer (NSCLC) lacking actionable driver alterations. The update synthesizes data from recent clinical trials, emphasizing first-line combinations of immune checkpoint inhibitors with or without platinum-based chemotherapy to improve overall survival. For patients with high PD-L1 expression (≥50%), pembrolizumab monotherapy remains a standard, while doublet chemotherapy plus immunotherapy is recommended for others. These guidelines offer clinicians a practical framework for navigating complex treatment algorithms to optimize outcomes in advanced oncology.
10.1200/JCO-26-00842
May 18 – May 25, 2026
Overcoming Primary and Acquired Resistance to Immunotherapy in Non-Small Cell Lung Cancer: Mechanisms, Challenges, and Emerging Strategies.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This review article summarizes current understanding of acquired resistance (AR) to immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) and highlights emerging therapeutic strategies. Key mechanisms of AR include impaired antigen presentation, T-cell exhaustion, and tumor microenvironment remodeling. Novel approaches under investigation involve next-generation ICIs (e.g., TIGIT, LAG-3), epigenetic modulators, metabolic agents, and cellular immunotherapies. The study emphasizes the need for biomarker-driven patient selection and rational combinations to overcome AR, aiming for more durable and personalized immunotherapy outcomes in NSCLC practice.
10.1200/JCO-25-03026
Biomarker-Based Eligibility for Lung Cancer Screening: Validation of the Protein-Based INTEGRAL-Risk Model.
JAMA-J AM MED ASSOC · Q1 JOURNAL - RANK #4/332TOP-TIER
This study developed and validated the protein-based INTEGRAL-Risk model to improve lung cancer screening eligibility in individuals with a smoking history. Using a large cohort (n=3695) across multiple regions, the model was trained and tested, demonstrating superior 1-year prediction (AUC 0.88) compared to the PLCOm2012 model (AUC 0.79; P<.001). It captured 85% of lung cancer cases versus 63% by USPSTF 2021 criteria at the same specificity. This model offers a practical advancement for identifying high-risk individuals, potentially enhancing the effectiveness of lung cancer screening programs.
10.1001/jama.2026.8044
May 11 – May 18, 2026
Temporal Trends in Lung Cancer Cases Diagnosed at Early Stage.
JAMA ONCOL · Q1 JOURNAL - RANK #14/326TOP-TIER
This descriptive surveillance study analyzed US Cancer Statistics data from 2003 to 2022, involving over 4.3 million cases, to evaluate temporal trends in early-stage lung cancer diagnoses following the 2013 USPSTF screening recommendations. Results show early-stage diagnoses rose from 17.6% in 2003 to 30.1% in 2022, with a notable sharp increase starting in 2015 (21.4%) through 2016 (24.6%). The findings highlight a significant shift toward earlier detection, which correlates with improved treatment efficacy and expanded therapeutic options for patients. Despite these gains, low screening uptake—reported at under 20% in 2024—suggests a critical need for clinicians to prioritize screening awareness and patient education to further improve cancer control outcomes.
10.1001/jamaoncol.2026.1199
May 04 – May 11, 2026
Rates of Systemic Treatment for Metastatic Non-Small Cell Lung Cancer Among Older Adults.
JAMA ONCOL · Q1 JOURNAL - RANK #14/326TOP-TIER
This population-based study analyzed SEER-Medicare data from 254,611 older adults diagnosed with metastatic non-small cell lung cancer (mNSCLC) between 2006 and 2021 to evaluate systemic treatment rates and associated factors. Results revealed that only 46.8% of patients received systemic therapy, with oncology referral (HR 2.5) and biomarker testing (+17.8% cumulative incidence) significantly increasing treatment likelihood. For clinicians, the study highlights that age over 80 and lack of specific histology (NSCLC-NOS) are major barriers, resulting in 15.4% and 12.8% lower treatment rates, respectively. Despite therapeutic advances, treatment rates have stagnated, suggesting a critical need to improve subspecialty access and biomarker utilization to address significant undertreatment in the geriatric oncology population.
10.1001/jamaoncol.2026.1080
Metastatic Trajectories in Non-Small Cell Lung Cancer Guide Local and Systemic Therapies.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This review introduces the concept of metastatic trajectories to characterize the spatiotemporal dynamics and intrapatient heterogeneity of metastatic non-small cell lung cancer (NSCLC). The framework shifts focus from static disease states to individual lesion behavior, analyzing genomic diversification and tumor-microenvironmental adaptation to explain divergent treatment responses. By utilizing biomarkers such as circulating tumor DNA and radiomic signatures, clinicians can track and predict trajectory evolution to refine the selection of local and systemic therapies. Integrating these trajectory-based assessments into clinical practice enables biology-informed treatment adaptation and provides a foundation for precision management in advanced cancer care.
10.1200/JCO-25-01958
Apr 27 – May 04, 2026
Lung cancer brain metastases management at the dawn of personalized medicine: are we ready to break the barriers?
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This review article summarizes the evolving management of lung cancer brain metastases (BM), a complication affecting nearly half of patients and significantly impairing survival. It highlights how advances in immune checkpoint inhibitors, next-generation CNS-penetrant targeted therapies, and stereotactic radiotherapy have reshaped the therapeutic landscape, improving intracranial control and patient outcomes. The integration of personalized systemic and local approaches offers new opportunities for optimizing central nervous system disease control. This emphasizes the need for individualized treatment strategies, addressing challenges in sequencing, patient selection, and risk-adapted approaches for future clinical trial design.
10.1016/j.annonc.2026.04.014
An agentic framework for autonomous scientific discovery in cancer pathology.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This study introduces SPARK, an agentic AI framework that uses natural language to autonomously generate biologically driven analytical tools for tumor pathology without extra model training. Evaluated across 18 cohorts with over 5,400 patients spanning five cancer types, SPARK produced clinically relevant concepts correlated with prognosis, pathological variables, and predictive biomarkers, including inferred tumor progression from static images. The framework directly addresses the clinician’s interest in cancer-focused research by demonstrating applicability in lung, colorectal, breast, and oropharyngeal cancers, with evidence of prognostic and predictive value. Primary implications include potential to enhance diagnostic precision and biological insight, though prospective clinical validation is still needed before routine use.
10.1038/s41591-026-04357-y
Tiragolumab Plus Atezolizumab and Chemotherapy for Advanced Nonsquamous Non-Small Cell Lung Cancer: The Phase 3 SKYSCRAPER-06 Randomized Clinical Trial.
JAMA ONCOL · Q1 JOURNAL - RANK #14/326TOP-TIER
The phase 3 SKYSCRAPER-06 trial evaluated tiragolumab plus atezolizumab plus chemotherapy versus placebo plus pembrolizumab plus chemotherapy as first-line treatment for advanced nonsquamous NSCLC in 542 previously untreated patients. The study found no significant improvement, with median progression-free survival of 8.3 months vs 9.9 months (HR 1.27; P=0.99) and overall survival of 18.9 months vs 23.1 months (HR 1.33; P=0.98). These negative results indicate the experimental regimen is not superior to the control arm. Clinically, this means the tiragolumab combination is not a recommended first-line option for this patient population.
10.1001/jamaoncol.2026.0818
Apr 20 – Apr 27, 2026
First-in-Human, Phase I Study of Sigvotatug Vedotin, an Integrin Beta-6-Directed Antibody-Drug Conjugate: Results From Dose Expansion in Advanced Non-Small Cell Lung Cancer.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This phase I dose-expansion study evaluated the safety and efficacy of sigvotatug vedotin (SV), a novel integrin beta-6-directed antibody-drug conjugate, in 117 patients with advanced non-small cell lung cancer (NSCLC). Results showed a manageable safety profile, with grade ≥3 adverse events occurring in 35% of patients receiving the optimized 1.8 mg/kg AiBW bi-weekly regimen. The overall objective response rate was 19%, which increased to 29% with a 12.8-month median duration of response in nonsquamous, taxane-naïve patients. These findings support the clinical development of SV as a targeted therapy for advanced lung cancer, particularly using adjusted ideal body weight dosing to minimize pharmacokinetic variability.
10.1200/JCO-25-02016
Apr 13 – Apr 20, 2026
Selpercatinib and the Crossover Conundrum: Potential Impact of Postprogression Therapies on Overall Survival.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This abstract addresses the critical challenge of interpreting overall survival (OS) in randomized cancer trials, particularly due to high crossover rates and varied postprogression therapies, using Study LIBRETTO-431 as a case study. LIBRETTO-431 was an ex-US multiregional, open-label, randomized trial comparing selpercatinib to chemoimmunotherapy in treatment-naïve advanced RET fusion-positive non-small cell lung cancer. While selpercatinib showed a large improvement in progression-free survival, the immature OS analysis yielded a hazard ratio of 1.26, favoring the chemoimmunotherapy arm. This highlights the need for prespecified plans for OS data collection and analytical methods in cancer trials to accurately account for postprogression therapies and ensure reliable interpretation for clinical practice.
10.1200/JCO-25-02375
Apr 06 – Apr 13, 2026
Outcomes and Treatments of Patients With Non-Small Cell Lung Cancer Who Received Pembrolizumab.
JAMA ONCOL · Q1 JOURNAL - RANK #14/326TOP-TIER
This nationwide, population-based, retrospective cohort study aimed to describe subsequent treatments and outcomes after 2 years of pembrolizumab discontinuation in patients with advanced non-small cell lung cancer (NSCLC) using French administrative health data. Among 1480 patients, the 48-month overall survival rate was 76.9% (95% CI, 72.7%-81.3%), and the time to next treatment or death rate was 49.9% (95% CI, 45.3%-55.0%) after pembrolizumab discontinuation. Only 26.1% (387 patients) received subsequent therapy, predominantly chemotherapy (51.7%) or radiotherapy (47.3%), with immunotherapy rechallenge being rare (1.0% of first treatments). These findings provide crucial real-world data on long-term outcomes and post-immunotherapy management for advanced NSCLC, suggesting high survival rates and infrequent immunotherapy rechallenge, which directly informs clinical practice.
10.1001/jamaoncol.2026.0669
Mar 30 – Apr 06, 2026
Interpretation of constitutional cancer predisposition gene variants in 14 765 individuals in the 100 000 Genomes Project cancer arm: a retrospective cohort analysis.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This retrospective cohort study assessed the frequency and nature of constitutional variants in 109 cancer predisposition genes among 14,765 patients with cancer in the UK health-care system. Key findings revealed that 711 (5%) participants harbored a pathogenic or likely pathogenic variant, with CHEK2 (0.82%) and BRCA2 (0.75%) being the most common, and ovarian cancer showing the highest proportion (9%) among specific tumor types. These results are highly relevant for clinicians as they provide a comprehensive understanding of the genetic landscape in cancer patients, informing genetic testing strategies and risk stratification. The study underscores the implications of more expansive genetic testing and the necessity of robust variant interpretation to optimize patient benefit and guide clinical service planning.
10.1016/S1470-2045(25)00766-1
Gotistobart or docetaxel in metastatic squamous non-small cell lung cancer: stage 1 of the randomized phase 3 PRESERVE-003 trial.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
The PRESERVE-003 stage 1 trial evaluated the preliminary efficacy and safety of gotistobart, a novel CTLA-4 antibody, versus docetaxel in patients with metastatic squamous non-small cell lung cancer (sqNSCLC) resistant to prior therapies. Patients were randomized 1:1 to gotistobart (N=45) or docetaxel (N=42). After a median follow-up of 14.5 months, median overall survival was not reached with gotistobart (95% CI 9.3 to not evaluable) compared to 10.0 months (95% CI 6.2 to 11.9 months) with docetaxel, yielding a hazard ratio of 0.46 (95% CI 0.25 to 0.84, P=0.0102). These findings are highly relevant to cancer research, offering a potential new therapeutic option for patients with advanced sqNSCLC who have exhausted standard treatments, with manageable safety (grade ≥3 treatment-related adverse events in 42% vs 49%). Gotistobart monotherapy shows promise in providing clinically meaningful survival benefit for this challenging patient population, warranting further investigation.
10.1038/s41591-026-04323-8
Mar 23 – Mar 30, 2026
Combination of Radiotherapy and Immunotherapy in Advanced Non-Small Cell Lung Cancer.
JAMA ONCOL · Q1 JOURNAL - RANK #14/326TOP-TIER
This territory-wide cohort study (OCEANUS) investigated real-world overall survival (OS) outcomes of sequential versus concurrent radiotherapy and immunotherapy (iRT), and the role of chemotherapy, in 335 patients with newly diagnosed advanced or refractory non-small cell lung cancer (NSCLC) in Hong Kong. For newly diagnosed advanced NSCLC, sequential iRT significantly prolonged median OS to 20.3 months (vs 16.0 months for concurrent; adjusted HR 0.68, P=.045), and chemotherapy was also associated with longer survival, while in refractory NSCLC, RT with ICI maintenance showed a numerically longer, but non-significant, median OS of 11.2 months (vs 6.7 months without; P=.20). This research directly addresses optimal treatment strategies for advanced NSCLC, a major cancer type, providing real-world evidence on sequencing iRT and the utility of chemotherapy, which is highly relevant to cancer care. These hypothesis-generating findings suggest potential benefits of sequential iRT and chemotherapy in newly diagnosed advanced NSCLC, supporting the need for prospective randomized studies to define optimal treatment guidelines.
10.1001/jamaoncol.2026.0392
Setidegrasib in Advanced Non-Small-Cell Lung Cancer and Pancreatic Cancer.
NEW ENGL J MED · Q1 JOURNAL - RANK #2/332TOP-TIER
This phase 1 study evaluated the safety and antitumor activity of setidegrasib, a novel KRAS G12D-targeted protein degrader, in 203 patients with previously treated advanced solid tumors, primarily non-small-cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma. At the 600 mg dose, 36% of 45 NSCLC patients achieved a partial response with a median progression-free survival of 8.3 months, while 24% of 21 metastatic pancreatic ductal adenocarcinoma patients had a response with a median progression-free survival of 3.0 months. These findings demonstrate promising antitumor activity for setidegrasib in advanced KRAS G12D-mutated NSCLC and pancreatic cancer, addressing a critical unmet need for targeted therapies. The study implies setidegrasib could be a significant therapeutic option, warranting further investigation in later-phase trials for these specific cancer populations.
10.1056/NEJMoa2600752
Implementation of the NHS England Lung Cancer Screening Programme over 5 years.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This study presents the progress and outcomes of the NHS England Lung Cancer Screening Programme, a national initiative offering low-dose computed tomography to high-risk individuals aged 55-74. By March 2025, the program invited over two million people, leading to the diagnosis of 7,193 lung cancers, with 63.1% identified at stage 1 and 12.6% at stage 2. These efforts significantly increased the early-stage proportion of lung cancer in England, particularly in underserved regions, demonstrating the program’s feasibility and scalability. The findings support the global adoption of lung cancer screening and provide practical insights for international implementation, despite ongoing needs to address participation inequalities.
10.1038/s41591-026-04292-y
Survival outcome of VATS compared with open lobectomy for lung cancer: an individual patient data meta-analysis of randomised trials.
LANCET · Q1 JOURNAL - RANK #1/332TOP-TIER
This individual patient data meta-analysis of three randomized trials compared VATS versus open lobectomy for early-stage NSCLC, finding that VATS provided a 21% reduction in mortality risk (HR 0.79, 95% CI 0.65-0.96) with similar disease-free survival (HR 0.91, 95% CI 0.75-1.12). The study directly addresses oncological outcomes in lung cancer surgery, which is the clinician’s primary interest in cancer-focused research. These results provide high-level evidence supporting the oncological superiority of VATS for surgical resection. The findings suggest that VATS should be prioritized when technically feasible for early-stage NSCLC patients.
10.1016/S0140-6736(26)00031-0
Mar 16 – Mar 23, 2026
MTAP Loss Is Frequent in Oncogene-Driven NSCLC and May Confer Sensitivity to Combined PRMT5 Inhibitors and Targeted Therapies.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This study investigated the frequency and therapeutic relevance of MTAP loss in over 13,000 oncogene-driven non-small cell lung cancer (NSCLC) samples and evaluated the efficacy of a PRMT5 inhibitor, BMS-986504, alone and in combination with targeted therapies in preclinical models. MTAP loss was frequent in ALK-rearranged (27-45%), RET-rearranged (18.5-35%), and EGFR-mutant NSCLC (17-29%), but did not impact first-line targeted therapy outcomes; however, BMS-986504 showed nanomolar activity in 11/18 MTAP-deleted models and synergistic effects with targeted therapies in 11/18 models, improving antitumor activity in resistant ex vivo and in vivo models. The findings are highly relevant to cancer clinicians by identifying MTAP loss as a potential biomarker for a therapeutic vulnerability in specific NSCLC subtypes, particularly in cases of resistance to current targeted therapies. This suggests that MTA-cooperative PRMT5 inhibition could be a promising strategy to enhance targeted therapy efficacy in MTAP-deleted, oncogene-driven NSCLC, offering new avenues for treatment development.
10.1016/j.annonc.2026.03.001
Mar 09 – Mar 16, 2026
Benmelstobart plus anlotinib versus pembrolizumab as first-line treatment for PD-L1-positive, advanced non-small-cell lung cancer (CAMPASS): a blinded, randomised, controlled, phase 3 trial.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This blinded, randomized, phase 3 trial (CAMPASS) evaluated the efficacy and safety of benmelstobart plus anlotinib compared to pembrolizumab monotherapy as a first-line treatment for 531 patients with PD-L1-positive, advanced non-small-cell lung cancer. The combination therapy significantly improved median progression-free survival to 11.0 months compared to 7.1 months for pembrolizumab (HR 0.70, p=0.0057), though grade 3 or worse treatment-related adverse events were more frequent in the combination group (59% vs. 29%). For clinicians treating advanced lung cancer, these results demonstrate that combining a PD-L1 inhibitor with an anti-angiogenic agent provides superior disease control over standard immunotherapy alone in driver-negative populations. While the combination presents a potential new first-line option, the increased toxicity profile—particularly hypertension and hemoptysis—requires careful patient selection and monitoring in clinical practice.
10.1016/S1470-2045(26)00049-5
Aumolertinib with carboplatin-pemetrexed versus aumolertinib for nonsmall cell lung cancer with EGFR and concomitant tumor suppressor genes (ACROSS2): An open-label, multicenter, randomized phase 3 study.
CA-CANCER J CLIN · Q1 JOURNAL - RANK #1/326TOP-TIER
The ACROSS2 study, a phase 3 randomized trial, investigated aumolertinib plus carboplatin-pemetrexed versus aumolertinib monotherapy in 126 patients with advanced, EGFR-mutated nonsmall cell lung cancer (NSCLC) and concomitant tumor suppressor gene mutations. At a median follow-up of 25.3 months, combination therapy significantly prolonged median progression-free survival (PFS) to 19.78 months compared to 16.53 months for monotherapy (HR, 0.58; 95% CI, 0.34-0.97), with a clear PFS benefit in patients with co-existing TP53 mutations. This research directly addresses a critical need in cancer treatment by identifying an intensified strategy for a challenging subset of NSCLC patients, thereby improving outcomes in a specific cancer population. The findings support a genotype-directed, chemotherapy-targeted intensification approach, suggesting that aumolertinib combined with carboplatin-pemetrexed could become a preferred first-line option for this molecularly defined patient group.
10.3322/caac.70071
Mar 02 – Mar 09, 2026
Cardiac radiosensitivity in the era of thoracic chemoradiotherapy and immunotherapy: a scoping review.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This scoping review examines cardiac toxicity associated with concurrent chemoradiotherapy and immune checkpoint inhibitor (ICI) consolidation, which is standard of care for unresectable stage III non-small-cell lung cancer (NSCLC) and other thoracic malignancies. It synthesizes findings from ten clinical studies, two reviews, and five preclinical reports to address six key questions regarding cardiac risks and mitigation strategies. While no specific numerical results are provided, the review highlights the new cardiac risk profile from combined therapies, emphasizing the need for larger, long-term studies. This research is highly relevant for clinicians managing cancer patients, as understanding and mitigating these toxicities is crucial for balancing oncological efficacy with cardiovascular safety in practice.
10.1016/S1470-2045(25)00651-5
Osimertinib plus datopotamab deruxtecan in patients with EGFR-mutated advanced NSCLC post-progression on first-line osimertinib: ORCHARD.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This Phase II platform study (ORCHARD) evaluated the efficacy and safety of combining osimertinib with the anti-TROP2 antibody-drug conjugate datopotamab deruxtecan (Dato-DXd) in patients with EGFR-mutated advanced NSCLC who progressed on first-line osimertinib. In the 6 mg/kg cohort, the confirmed objective response rate was 36%, with a median progression-free survival of 11.7 months and a median overall survival of 26.2 months. The study directly addresses the clinical challenge of managing resistance to first-line EGFR tyrosine kinase inhibitors in lung cancer patients, providing specific evidence for a novel combination strategy. While the 6 mg/kg dose showed higher toxicity with 76% grade ≥3 adverse events, it is suggested as the preferred starting dose due to superior duration of response and overall survival compared to the 4 mg/kg dose.
10.1016/j.annonc.2026.02.014