Non-Small Cell Lung Cancer
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Jul 13 – Jul 20, 2026
Durvalumab With Radiation Therapy in Patients With Inoperable Locally Advanced Non-Small Cell Lung Cancer Ineligible for Concurrent Chemoradiotherapy (DART).
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
The DART study investigated concurrent and consolidative durvalumab with definitive radiation therapy for cCRT-ineligible patients with inoperable, locally advanced non-small cell lung cancer (LA-NSCLC) in a multicenter, single-arm, prospective phase II trial. The study met its primary endpoint, demonstrating a 2-year progression-free survival of 39% compared to historical 20%, with a 2-year overall survival of 54%. Grade 3/4 treatment-related adverse events occurred in 21% of patients. This offers a promising new treatment option for a vulnerable LA-NSCLC patient population lacking a standard of care, directly impacting oncology practice.
10.1200/JCO-25-02517
Jul 06 – Jul 13, 2026
Lung Transplant for Refractory Lung-Limited Stage IV Non-Small Cell Lung Cancer.
JAMA-J AM MED ASSOC · Q1 JOURNAL - RANK #4/332TOP-TIER
This prospective, single-center registry study investigated the overall survival of 17 selected patients with medically refractory, lung-limited, stage IV non-small cell lung cancer (NSCLC) who underwent lung transplant compared to 81 similar patients receiving medical management alone. The 1-year overall survival was significantly higher for transplant recipients (100.0%) versus medical management (40.8%), an absolute difference of 59.2 percentage points. This research directly addresses a critical cancer-related question, demonstrating favorable early survival outcomes for a previously untreatable advanced NSCLC population. Lung transplant may offer a viable, life-extending option for carefully selected patients with refractory, lung-limited stage IV NSCLC, challenging historical treatment paradigms.
10.1001/jama.2026.8717
Jun 29 – Jul 06, 2026
Differential impact of proton pump inhibitors and antibiotics on immunotherapy efficacy after chemoradiotherapy in locally advanced non-small-cell lung cancer: a post-hoc analysis of the PACIFIC trial.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This post-hoc analysis of the PACIFIC trial investigated the impact of baseline proton pump inhibitors (PPIs) and antibiotics on durvalumab efficacy in 660 patients with unresectable stage III non-small cell lung cancer (NSCLC) after chemoradiotherapy. In the durvalumab group, PPI exposure significantly shortened progression-free survival (9.4 vs 17.2 months; HR 1.57; p<0.0001) and overall survival (33.0 vs 57.9 months; HR 1.66; p<0.0001). Antibiotic exposure also reduced progression-free survival (9.2 vs 15.6 months; HR 1.50; p=0.016) but not overall survival. These findings suggest that baseline PPI and antibiotic use may attenuate the benefit of durvalumab in NSCLC, highlighting a critical consideration for clinical practice.
10.1016/S1470-2045(26)00191-9
Improving neoadjuvant and perioperative therapy in non-small-cell lung cancer.
NAT REV CLIN ONCOL · Q1 JOURNAL - RANK #2/326TOP-TIER
This review summarizes current evidence and future directions for optimizing neoadjuvant and perioperative chemoimmunotherapy in early-stage, resectable non-oncogene-driven non-small-cell lung cancer (NSCLC). It highlights that this approach has become standard of care, demonstrating substantial increases in pathological response rates and improvements in overall survival, with pathological complete response (pCR) identified as a robust surrogate for durable benefit. The review explores integrating complementary tools like circulating tumor DNA, radiomics, and biomarkers to refine patient selection and dynamically adapt perioperative strategies. This aims to intensify treatment for high-risk populations, increase pCR likelihood, and improve disease control, offering critical implications for personalized NSCLC management.
10.1038/s41571-026-01174-7
Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2026.3.2.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This abstract describes the ASCO Living Guideline, Version 2026.3.2, for therapy in Stage IV Non-Small Cell Lung Cancer (NSCLC) with driver alterations. These guidelines are developed by a standing expert panel through continuous, systematic review of rapidly evolving health literature to inform clinical practice. The primary objective is to provide updated recommendations for NSCLC treatment, adapting to new evidence. While not a primary research study, it offers crucial, evidence-based guidance for clinicians managing cancer patients, directly aligning with interests in cancer-focused research.
10.1200/JCO-26-01479
Jun 15 – Jun 22, 2026
Bispecific Antibody Ivonescimab Added to Chemotherapy in EGFR-Variant Non-Small Cell Lung Cancer: The HARMONi-A Randomized Clinical Trial.
JAMA-J AM MED ASSOC · Q1 JOURNAL - RANK #4/332TOP-TIER
This Phase 3 randomized trial evaluated the efficacy of adding ivonescimab, a bispecific antibody targeting PD-1 and VEGF, to pemetrexed and carboplatin in 322 patients with EGFR-variant NSCLC following TKI progression. Ivonescimab significantly improved median overall survival to 16.8 months compared to 14.1 months with chemotherapy alone (HR 0.74; 95% CI, 0.58-0.95; P = .02). The treatment demonstrated a 2.7-month absolute survival benefit and a higher 30-month survival rate of 29.1% versus 18.4%, directly addressing the clinician’s interest in advanced oncological interventions. Despite a higher incidence of grade 3 or greater adverse events (67.1% vs 54.7%), this combination offers a clinically meaningful survival advantage for a high-need cancer population.
10.1001/jama.2026.7745
Plasma proteomic signatures of cellular aging predict human disease.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This study utilized machine learning models on plasma proteomic data from 60,542 individuals to estimate the biological age of over 40 distinct cell types. Researchers found that extreme respiratory epithelial cell aging in smokers was associated with a 58% higher lung cancer risk compared to smoking alone, alongside significant associations for Alzheimer’s and ALS. For clinical oncology, these proteomic signatures provide a novel method for stratifying cancer risk by quantifying cellular-level physiological decline. The findings establish a framework for using cellular aging trajectories to predict disease susceptibility and mortality over a 15-year follow-up period.
10.1038/s41591-026-04446-y
Aumolertinib with or without chemotherapy in EGFR-mutated advanced non-small-cell lung cancer (AENEAS2): an open-label, multicentre, randomised, controlled, phase 3 trial.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This phase 3 trial (AENEAS2) evaluated aumolertinib with or without platinum-based chemotherapy as first-line treatment for advanced EGFR-mutated NSCLC. In 624 patients, median progression-free survival was significantly longer with combination therapy (28.9 months) versus monotherapy (18.9 months; HR 0.47, p<0.0001). This directly addresses the clinician’s interest in cancer research, specifically focused on improving outcomes in EGFR-mutant NSCLC. The regimen substantially delays progression but increases toxicity, requiring management per clinical practice; overall survival data are pending.
10.1016/S1470-2045(26)00090-2
Jun 08 – Jun 15, 2026
Electronic cigarette use after smoking cessation and lung cancer risk.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This large-scale cohort study of over 4.5 million Korean adults evaluated the association between post-cessation electronic cigarette use and lung cancer risk among former conventional smokers. Compared to complete quitters, e-cigarette users faced significantly higher risks of lung cancer incidence (aHR 1.56, 95% CI 1.24-1.97) and lung cancer-specific death (aHR 2.00, 95% CI 1.28-3.15). These associations remained consistent across both short-term and long-term quitters, with particularly pronounced risks observed in high-risk subgroups. The findings suggest that e-cigarette use may diminish the oncological benefits of smoking cessation, highlighting the clinical importance of promoting complete nicotine abstinence for lung cancer prevention.
10.1038/s41591-026-04469-5
Jun 01 – Jun 08, 2026
PD-(L)1 Inhibitor Monotherapy vs Chemoimmunotherapy for Advanced NSCLC With High PD-L1 Expression: A Systematic Review and Meta-Analysis.
JAMA ONCOL · Q1 JOURNAL - RANK #14/326TOP-TIER
This systematic review and meta-analysis of 24 phase 3 randomized clinical trials, involving 5546 patients, compared PD-(L)1 inhibitor monotherapy versus chemoimmunotherapy for treatment-naive advanced non-small cell lung cancer (NSCLC) with high PD-L1 expression. The study found that chemoimmunotherapy significantly improved overall survival (median OS 29.2 months vs 19.8 months) and progression-free survival (median PFS 11.3 months vs 6.8 months) compared to PD-(L)1 inhibitor monotherapy. These findings suggest that chemoimmunotherapy offers superior survival benefits for this specific patient population. This research directly informs first-line treatment decisions in advanced NSCLC, aiming to optimize patient outcomes.
10.1001/jamaoncol.2026.1548
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