Lung Cancer最新文献

{"title":"Response to the letter of Peng Bai and Jun Zhang on Cost-effectiveness of Adjuvant Alectinib in ALK-positive NSCLC—Considerations for Broader Applicability","authors":"Romain Supiot , Léopoldine du Manoir de Juaye , Christos Chouaid","doi":"10.1016/j.lungcan.2026.108944","DOIUrl":"10.1016/j.lungcan.2026.108944","url":null,"abstract":"","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"213 ","pages":"Article 108944"},"PeriodicalIF":4.4,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunotherapy in uncommon EGFR-mutant NSCLC: Revisiting a therapeutic gray zone","authors":"Jun Hyeok Lim, Woo Kyung Ryu, Jeong-Seon Ryu","doi":"10.1016/j.lungcan.2026.108938","DOIUrl":"10.1016/j.lungcan.2026.108938","url":null,"abstract":"","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"213 ","pages":"Article 108938"},"PeriodicalIF":4.4,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146189527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world occurrence of severe gastrointestinal bleeding in patients receiving amivantamab plus lazertinib: A two-case series among 25 consecutive cases","authors":"Kosuke Hashimoto,&nbsp;Masakazu Takahara,&nbsp;Reina Ishii,&nbsp;Tatsuhiko Uno,&nbsp;Ou Yamaguchi,&nbsp;Atsuto Mouri,&nbsp;Hisao Imai,&nbsp;Hiroshi Kagamu,&nbsp;Kyoichi Kaira","doi":"10.1016/j.lungcan.2026.108947","DOIUrl":"10.1016/j.lungcan.2026.108947","url":null,"abstract":"<div><div>Amivantamab plus lazertinib is an emerging targeted therapy directed against epidermal growth factor receptor (EGFR) and mesenchymal–epithelial transition pathways for the treatment of <em>EGFR</em>-mutated non-small cell lung cancer. Although clinical trials have not reported significant gastrointestinal bleeding (GIB), we describe two real-world cases (representing 8% of 25 treated patients) who developed life-threatening GIB during therapy. Both patients exhibited progressive hypoalbuminemia and gastrointestinal mucosal edema preceding the onset of bleeding. Contrast-enhanced computed tomography and endoscopic evaluation demonstrated diffuse bowel wall edema and multiple mucosal ulcers. Both the patients received apixaban. One patient recovered with supportive management, while the other died of hemorrhagic shock. These findings suggest that real-world patients, who are often older, treated in later lines of therapy, and using concomitant anticoagulants, may be more vulnerable to severe gastrointestinal complications than those enrolled in controlled clinical trials. Close monitoring of serum albumin levels and gastrointestinal symptoms is recommended to prevent potentially fatal complications.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"213 ","pages":"Article 108947"},"PeriodicalIF":4.4,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methodological considerations in assessing the clinical impact of TP53 classifications in advanced NSCLC","authors":"Xiaorong Lu,&nbsp;Shanshan Yuan","doi":"10.1016/j.lungcan.2026.108937","DOIUrl":"10.1016/j.lungcan.2026.108937","url":null,"abstract":"","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"213 ","pages":"Article 108937"},"PeriodicalIF":4.4,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting HGF/MET and CXCL1/CXCR2 axes bypasses resistance to KRASG12C inhibitors in NSCLC","authors":"A. Cavazzoni ,&nbsp;M. Pagano Mariano ,&nbsp;A. Palladini ,&nbsp;G. Digiacomo ,&nbsp;S. La Monica ,&nbsp;M. Bonelli ,&nbsp;M. Galetti ,&nbsp;I. Pace ,&nbsp;R. Roncarati ,&nbsp;E. Giovannetti ,&nbsp;P. Aretini ,&nbsp;R. Minari ,&nbsp;M. Treccani ,&nbsp;M. Pluchino ,&nbsp;C.A. Lagrasta ,&nbsp;S. Angelicola ,&nbsp;G. Mazzaschi ,&nbsp;P. Bordi ,&nbsp;F. Gelsomino ,&nbsp;F. Agustoni ,&nbsp;R. Alfieri","doi":"10.1016/j.lungcan.2026.108939","DOIUrl":"10.1016/j.lungcan.2026.108939","url":null,"abstract":"<div><h3>Background</h3><div>Resistance to KRAS^G12C inhibitors sotorasib and adagrasib, approved for KRAS^G12C-mutant advanced Non-Small Cell Lung Cancer (NSCLC), involves multiple subclonal events, raising significant concerns about overcoming the resistant phenotype. Cytokines, chemokines, and growth factors are key mediators of drug resistance and targeting their signaling pathways is an emerging strategy in cancer therapy.</div></div><div><h3>Methods</h3><div>We generated cell clones from KRAS^G12C-mutated NSCLC cells treated with KRAS inhibitors and cell cultures from a sotorasib-resistant patient-derived xenograft (PDX). Gene mutations and changes in gene expression were evaluated using NGS, RNAseq. The mRNA and protein levels encoded by the Hepatocyte Growth Factor (HGF) and CXCL1 genes were quantified using RT-PCR and ELISA assay. The effect of drug combination was obtained by the Sulforhodamine-B assay and analyzed by Combenefit Software. Cell death was detected by Annexin-V assay. Cell signaling and epithelial-to-mesenchymal transition were evaluated by Western blotting.</div></div><div><h3>Results</h3><div>NSCLC cell clones and PDX cell cultures with acquired and intrinsic resistance to KRAS^G12C inhibitors exhibited elevated levels of CXCL1 and HGF expression and secretion, with activation of CXCR2 and c-MET signalling pathways. The combination of CXCR2 and c-MET inhibitors led to synergistic inhibition of cell growth and reduced cell viability by inhibiting the ERK1/2 and AKT signalling pathways. This combination also reversed EMT and induced apoptosis in sotorasib- and adagrasib-resistant clones, regardless of the genetic alterations responsible for resistance.</div></div><div><h3>Conclusions</h3><div>CXCL1/CXCR2 and HGF/c-MET may represent compensatory pathways that sustain proliferation and survival in resistance to KRAS^G12C inhibitors. The simultaneous blockade of these signals may offer a novel strategy for bypassing resistance.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"213 ","pages":"Article 108939"},"PeriodicalIF":4.4,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic significance of consolidation-to-tumor ratio in stage IA solid predominant non-mucinous adenocarcinoma: a paradigm for risk stratification","authors":"Yura Ahn ,&nbsp;Geun Dong Lee ,&nbsp;SeHoon Choi ,&nbsp;Hyeong Ryul Kim ,&nbsp;Yong-Hee Kim ,&nbsp;Dong Kwan Kim ,&nbsp;Seung-Il Park ,&nbsp;Jooae Choe ,&nbsp;Jae Kwang Yun","doi":"10.1016/j.lungcan.2026.108934","DOIUrl":"10.1016/j.lungcan.2026.108934","url":null,"abstract":"<div><h3>Objective</h3><div>The optimal consolidation-to-tumor ratio (CTR) cutoff for survival stratification in radiologically solid-predominant adenocarcinoma (CTR &gt; 0.5) remains unclear. This study aimed to evaluate the prognostic significance of CTR in clinical-stage IA non-mucinous lung adenocarcinoma with CTR &gt; 0.5.</div></div><div><h3>Materials and methods</h3><div>We retrospectively analyzed patients who underwent curative resection for clinical stage IA non-mucinous adenocarcinoma with CTR &gt; 0.5 between 2011 and 2021. Optimal cutoffs for overall survival (OS) and freedom from recurrence (FFR) were determined using maximized log-rank statistics. Patients were stratified according to the derived CTR cutoff values, and OS and FFR were compared among the CTR groups before and after propensity score matching (PSM).</div></div><div><h3>Results</h3><div>Among 2,789 patients included, the optimal CTR cutoffs for OS and FFR were 0.84 and 0.85, respectively. Based on the 0.85 cutoff, patients were categorized into three groups: 0.5 &lt; CTR ≤ 0.85 (n = 672), 0.85 &lt; CTR &lt; 1 (n = 229), and CTR = 1 (n = 1,888). OS and FFR were significantly worse in the 0.85 &lt; CTR &lt; 1 group compared to the 0.5 &lt; CTR ≤ 0.85 group (p &lt; 0.05) but not significantly different from the CTR = 1 group (p &gt; 0.05). These trends persisted after PSM. The 0.85 &lt; CTR &lt; 1 group exhibited a higher proportion of pathological risk factors (high-grade patterns, lymphovascular invasion, and nodal metastasis) than the 0.5 &lt; CTR ≤ 0.85 group (all p &lt; 0.05) and was comparable to the CTR = 1 group, except for lymphovascular invasion (p = 0.045). Dichotomization into 0.5 &lt; CTR ≤ 0.85 and 0.85 &lt; CTR ≤ 1 revealed significantly worse OS and FFR in the 0.85 &lt; CTR ≤ 1 group across PSM cohorts for both lobectomy and sublobar resection.</div></div><div><h3>Conclusion</h3><div>A CTR cutoff of 0.85 effectively distinguishes survival outcomes in patients with clinical stage IA adenocarcinoma and CTR &gt; 0.5 and may inform risk stratification and postoperative surveillance.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"213 ","pages":"Article 108934"},"PeriodicalIF":4.4,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osimertinib dose-reduction and survival in 1L EGFR-mutated metastatic non-small cell lung cancer (mNSCLC)","authors":"Adam Barsouk ,&nbsp;Alec Heidlauf ,&nbsp;Keshav Goel ,&nbsp;Lynn Rushkin ,&nbsp;Anna Anran Huang ,&nbsp;Omar Elghawy ,&nbsp;Connie Yu ,&nbsp;Lucy Wang ,&nbsp;David Yang ,&nbsp;Martin Kurian ,&nbsp;Lauren Reed-Guy ,&nbsp;Lova Sun ,&nbsp;Aditi Singh ,&nbsp;Charu Aggarwal ,&nbsp;Roger B. Cohen ,&nbsp;Corey Langer ,&nbsp;Melina E. Marmarelis","doi":"10.1016/j.lungcan.2026.108936","DOIUrl":"10.1016/j.lungcan.2026.108936","url":null,"abstract":"<div><h3>Introduction</h3><div>Osimertinib has become standard of care<!--> <!-->in 1 L<!--> <em>EGFR</em>-<!--> <!-->mutated(mt)<!--> <!-->mNSCLC following the FLAURA trial.<!--> <!-->However, limited data are available on the effect of osimertinib dose-reduction<!--> <!-->on outcomes compared to<!--> <!-->full-dose.</div></div><div><h3>Methods</h3><div>We performed a single-institution, retrospective analysis of pts with<!--> <em>EGFR</em>-mt mNSCLC treated with 1 L osimertinib from 2018 to 2023. Pts who underwent dose-reduction were compared to those<!--> <!-->maintained on full dose (80 mg daily). Baseline demographics, disease characteristics, treatment history, toxicity, and clinical outcomes were abstracted from the electronic medical record and compared using independent sample t-tests and chi-square analyses as appropriate. Median progression free survival (mPFS), time to discontinuation (mTTD), and overall survival (mOS) were compared via Kaplan-Meier log-rank test and Cox regression analysis with time-varying covariate.</div></div><div><h3>Results</h3><div>Of 171 pts with mNSCLC treated with 1 L osimertinib, 26 (15%) required dose-reduction. Sex (p = 0.458), race (p = 0.421), ECOG PS &gt; 1 at diagnosis (p = 0.730) and smoking history (p = 0.485) were comparable between reduced-dose and full-dose pts. 44% vs 34% of reduced dose and full dose pts, respectively, had CNS metastases at diagnosis (p = 0.192). All dose-reduced pts experienced adverse events (AEs), compared to 48% of full-dose pts (p &lt; 0.001). Dose-reduced pts had shorter mPFS compared to full-dose pts (17.0 vs 24.6 mos; p = 0.043). Median PFS with dose-reduction was shorter compared to full-dose in pts with (p = 0.041) or without CNS metastases (p = 0.048). On time-variate, multivariable analysis, dose-reduction was associated with inferior PFS (p = 0.047) regardless of baseline characteristics. TTD was comparable in pts with and without dose-reduction (21.3 vs 25.2 mos; p = 0.521) OS was comparable in pts with and without dose-reduction (36.7vs 39.2 mos; p = 0.749). 14 pts (8%) discontinued osimertinib due to AEs, of whom 9 (64%) were previously dose-reduced. mPFS was comparable (p = 0.334) between pts who discontinued and those who did not, as was mOS (p = 0.910).</div></div><div><h3>Conclusion</h3><div>Dose-reduction of osimertinib was relatively uncommon and associated with shorter PFS (primarily<!--> <!-->CNS progression), but similar TTD and OS in 1 L patients with<!--> <em>EGFR</em>-mutated mNSCLC.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"213 ","pages":"Article 108936"},"PeriodicalIF":4.4,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune-related disorders in patients with Thymic Epithelial Tumors: from pathogenesis to tailored interventions","authors":"Erica Pietroluongo ,&nbsp;Giovannella Palmieri ,&nbsp;Paolo Antonio Ascierto ,&nbsp;Margaret Ottaviano","doi":"10.1016/j.lungcan.2026.108915","DOIUrl":"10.1016/j.lungcan.2026.108915","url":null,"abstract":"<div><h3>Background and objective</h3><div>Thymic epithelial tumors (TETs) are rare malignancies often associated with immunological disorders (IDs), including autoimmune diseases and paraneoplastic syndromes. Myasthenia gravis (MG) is the most frequently reported condition, although other IDs can manifest across various organ systems. This review aims to give an overview of the current knowledge on the epidemiology, pathogenesis, and management of IDs associated with TETs, emphasizing their prognostic impact and challenges in clinical practice.</div></div><div><h3>Methods</h3><div>We performed a narrative review using PubMed and Embase databases to identify relevant literature published between January 1971 and October 2024. Keywords included “thymic epithelial tumors”, “immunological disorders,” “autoimmune diseases,” and “paraneoplastic syndromes.” Only peer-reviewed articles in English were included.</div></div><div><h3>Key content and findings</h3><div>This review examines the association of TETs with the most frequent IDs, including MG, pure red cell aplasia, and Good’s syndrome. The prognostic implications of IDs in TETs remain unclear, and the available literature presents conflicting data. While some studies suggest correlations with favourable outcomes, others fail to establish IDs as independent prognostic factors for recurrence-free survival (RFS) or overall survival (OS).</div></div><div><h3>Conclusions</h3><div>The management of TETs with associated IDs requires a multidisciplinary approach that integrates tumor-specific treatments and tailored interventions for immune-related disorders. Advances in understanding molecular mechanisms have shed light on their pathogenesis. Nevertheless, gaps persist regarding prognostic implications and long-term management. Future efforts should focus on identifying predictive biomarkers for immune complications, optimizing therapies, and enhancing international data collection to clarify the impact of IDs on patient outcomes.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"213 ","pages":"Article 108915"},"PeriodicalIF":4.4,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146029993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FAM83A promotes the progression of lung squamous cell carcinoma by inducing the epithelial–mesenchymal transition and inhibiting apoptosis via ERK pathway","authors":"Xiang Fei ,&nbsp;Hao Wu ,&nbsp;Mengxing Li ,&nbsp;Jianmang Yu ,&nbsp;Junyi Huang ,&nbsp;Siqi Cao ,&nbsp;Shiyou Wei ,&nbsp;Qiuyun Wang ,&nbsp;Wei Zhu ,&nbsp;Zhize Yuan","doi":"10.1016/j.lungcan.2026.108917","DOIUrl":"10.1016/j.lungcan.2026.108917","url":null,"abstract":"<div><h3>Background</h3><div>The protein Family with Sequence Similarity 83, Member A (FAM83A) is associated with the advancement of various tumors. This study examines the biological function and fundamental processes of FAM83A in lung squamous cell carcinoma (LUSC).</div></div><div><h3>Methods</h3><div>The GSE33479 dataset was used to compare FAM83A expression levels in LUSC, while the GSE73403 dataset explored its prognostic relevance. FAM83A was knocked down or over-expressed in LUSC cell lines, and CCK-8, colony formation, Transwell, and flow cytometry assays were performed to evaluate the effects of altered FAM83A expression on LUSC cell proliferation, apoptosis, invasion, and migration. Organoids and animal models were utilized to validate the impact of FAM83A knockdown on tumor growth. Finally, FAM83A-overexpressing LUSC cells were treated with SCH772984, a specific ERK inhibitor, to elucidate the potential mechanism underlying the oncogenic effect of FAM83A.</div></div><div><h3>Results</h3><div>FAM83A was upregulated in LUSC tissues and cell lines, with high expression correlating with shorter overall survival. Depletion of FAM83A reduced the migration, invasion, and proliferation of LUSC cells, accompanied by cell cycle arrest and increased apoptotic rate. Western blotting analyses showed that FAM83A knockdown upregulated E-cadherin, BAX, and Cleaved-PARP/Caspase 3, while downregulating N-cadherin, Vimentin, BCL2, and Cyclin D1. Conversely, overexpression of FAM83A in LUSC cells yielded the opposite phenotypes. In both organoid cultures and in vivo models, inhibition of FAM83A attenuated tumor growth. Rescue experiments demonstrated that SCH772984 reversed the malignant phenotypes induced by FAM83A over-expression, indicating that FAM83A promoted cell cycle progression, inhibits apoptosis, and enhances epithelial-mesenchymal transition (EMT) in LUSC through activating the ERK signaling pathway.</div></div><div><h3>Conclusion</h3><div>FAM83A is crucial in the advancement and spread of LUSC, as it promotes EMT and inhibits apoptosis via the activation of the ERK pathway. These findings highlight its potential as a strategic molecular target for the treatment of LUSC.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"213 ","pages":"Article 108917"},"PeriodicalIF":4.4,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145981116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KRAS-mutant advanced NSCLC: efficacy and clinical outcomes from network meta-analysis and real-world evidence","authors":"Xiaoyu Gang ,&nbsp;Yige Sun ,&nbsp;Junli Hao ,&nbsp;Suya Zhao ,&nbsp;Yizheng Wang ,&nbsp;Xinrui Yang ,&nbsp;Heming Li ,&nbsp;Mingfang Zhao","doi":"10.1016/j.lungcan.2026.108930","DOIUrl":"10.1016/j.lungcan.2026.108930","url":null,"abstract":"<div><h3>Background</h3><div><em>KRAS</em> is a common driver gene in non-small cell lung cancer (NSCLC). Owing to the absence of universally effective targeted agents and marked heterogeneity, optimal treatment selection for <em>KRAS</em>-mutant NSCLC remains uncertain. This study combined network meta-analysis (NMA) with real-world evidence to inform precision treatment strategies.</div></div><div><h3>Methods</h3><div>Thirteen randomized controlled trials were included in a Bayesian NMA to compare efficacy outcomes across regimens in <em>KRAS</em>-mutant and <em>KRAS</em> G12C-mutant NSCLC. In parallel, real-world data from advanced <em>KRAS</em>-mutant NSCLC patients treated at our center were analyzed.</div></div><div><h3>Results</h3><div>Across <em>KRAS</em> and G12C NMAs, immunotherapy-based regimens generally outperformed chemotherapy-based regimens. PD-(L)1 inhibitors monotherapy ranked highest for overall survival (OS), while chemotherapy plus PD-(L)1 inhibitors and anti-angiogenic therapy (anti-VEGF) ranked highest for progression-free survival (PFS). Chemotherapy plus dual immune checkpoint blockade (PD-(L)1 and CTLA-4) yielded a greater improvement in OS than in PFS. In our real-world cohort, first-line PD-(L)1 monotherapy achieved the best outcomes (objective response rate: 88.9%; median PFS: 22.2 months), followed by chemotherapy plus PD-(L)1 ± anti-VEGF. On multivariable analysis, ECOG performance status 0–1, PD-L1 TPS ≥ 50%, TMB ≥ 10 mut/Mb, and chemotherapy plus PD-(L)1 ± anti-VEGF were independently associated with longer first-line PFS. In subsequent lines, G12C inhibitors significantly improved outcomes versus other therapies, whereas non-G12C disease derived limited benefit from available strategies.</div></div><div><h3>Conclusions</h3><div>Immunotherapy constitutes the cornerstone of first-line therapy for <em>KRAS</em>-mutant NSCLC. Within this framework, PD-(L)1 monotherapy may be appropriate for carefully selected patients with high PD-L1 expression, whereas chemoimmunotherapy can extend benefit to broader subgroups; escalation with anti-VEGF or anti-CTLA-4 agents appears clinically promising and merits biomarker-driven prospective evaluation. KRAS G12C inhibitors are effective in later lines, while treatment options for non-G12C disease remain limited.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"213 ","pages":"Article 108930"},"PeriodicalIF":4.4,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145981781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}