Lung Cancer最新文献

{"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":"2026-03-01","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":"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 ,&nbsp;Léopoldine du Manoir de Juaye ,&nbsp;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":"2026-03-01","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":"Prevention and management of amivantamab-induced dermatologic toxicities: a European expert consensus and practical algorithm","authors":"Nikolaou Vasiliki ,&nbsp;Sibaud Vincent ,&nbsp;Apalla Zoe ,&nbsp;Starace Michela ,&nbsp;Mayor Ander ,&nbsp;Giacchero Damien ,&nbsp;Sollena Pietro ,&nbsp;Fattore Davide ,&nbsp;Malissen Nausicaa","doi":"10.1016/j.lungcan.2026.108950","DOIUrl":"10.1016/j.lungcan.2026.108950","url":null,"abstract":"<div><h3>Background</h3><div>Amivantamab, a bispecific antibody targeting EGFR and MET, is increasingly used in advanced non–small cell lung cancer. Dermatologic and mucosal adverse events are highly prevalent and often more severe and clinically complex than with conventional EGFR inhibitors, frequently challenging treatment continuation. However, structured management guidelines for amivantamab-associated toxicities are currently lacking.</div></div><div><h3>Methods</h3><div>An international panel of dermatologists with expertise in oncodermatology and members of the EADV Task Force “Dermatology for Cancer Patients” conducted a structured review of clinical trial data, emerging real-world evidence, and existing toxicity management frameworks. Key clinical challenges were identified through iterative expert discussions, and consensus was achieved through repeated rounds of manuscript review and refinement. Pragmatic grading systems and stepwise management algorithms were developed.</div></div><div><h3>Results</h3><div>We propose comprehensive strategies for prevention and monitoring and provide toxicity-specific management algorithms for acneiform eruption, erosive pustular dermatosis (EPD)-like scalp reactions, paronychia, anogenital ulcerations, and mucositis. For EPD-like scalp eruptions and anogenital ulcerations, where validated grading systems are lacking, we introduce pragmatic severity-based grading frameworks. Emphasis is placed on early recognition, individualized supportive care, appropriate use of systemic therapies, and timely treatment modification to minimize unnecessary interruptions while ensuring patient safety.</div></div><div><h3>Conclusions</h3><div>Amivantamab is associated with a distinctive and clinically impactful toxicity profile that frequently complicates routine management. These consensus-based recommendations provide thoracic oncologists with practical tools to support early intervention, optimized supportive care, and rational treatment adaptation, potentially improving quality of life, reducing avoidable treatment interruptions, and supporting sustained oncologic benefit.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"213 ","pages":"Article 108950"},"PeriodicalIF":4.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165870","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":"2026-03-01","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":"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":"2026-03-01","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":"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":"2026-03-01","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":"Corrigendum to “Radiotherapy outcomes in patients with interstitial lung disease and interstitial lung abnormalities: Adverse events and survival from a UK tertiary centre” [Lung Cancer 211 (2026) 108873","authors":"Sarah Bowen Jones ,&nbsp;Gerard Gurumurthy ,&nbsp;Conal Hayton ,&nbsp;Ahmad Lodhi ,&nbsp;Aqeel Umar ,&nbsp;Corinne Faivre-Finn","doi":"10.1016/j.lungcan.2026.108942","DOIUrl":"10.1016/j.lungcan.2026.108942","url":null,"abstract":"","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"213 ","pages":"Article 108942"},"PeriodicalIF":4.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146092913","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,&nbsp;Woo Kyung Ryu,&nbsp;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":"2026-03-01","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":"Durvalumab-containing treatment for recurrent or metastatic pulmonary sarcomatoid carcinoma: A pooled post hoc analysis of two KCSG phase II trials","authors":"Dong Hyun Kim ,&nbsp;Miso Kim ,&nbsp;Jeonghwan Youk ,&nbsp;Tae Min Kim ,&nbsp;Gyeong-Won Lee ,&nbsp;Se Hyun Kim ,&nbsp;Yu Jung Kim ,&nbsp;Jin-Soo Kim ,&nbsp;Sook-Hee Hong ,&nbsp;Mi Sun Ahn ,&nbsp;Seong Hoon Shin ,&nbsp;Dong-Wan Kim ,&nbsp;Joo-Hang Kim ,&nbsp;Bhumsuk Keam","doi":"10.1016/j.lungcan.2026.108916","DOIUrl":"10.1016/j.lungcan.2026.108916","url":null,"abstract":"<div><h3>Introduction</h3><div>Pulmonary sarcomatoid carcinoma (PSC) is a rare cancer characterized by a high programmed death-ligand 1 (PD-L1) expression, suggesting a potential therapeutic benefit from immune checkpoint inhibitors. We investigated the efficacy of durvalumab-containing combination therapy and explored potential predictive biomarkers in patients with recurrent or metastatic (R/M) PSC.</div></div><div><h3>Method</h3><div>In this pooled <em>post hoc</em> analysis, data were integrated from two prospective phase II trials (NCT03022500 and NCT04224337) wherein durvalumab-containing combination therapies were evaluated in patients with R/M PSC. PD-L1 expression was assessed using 22C3 or SP263 assays, and circulating lymphocyte subsets were analyzed using flow cytometry.</div></div><div><h3>Results</h3><div>Overall, 33 patients were included, of whom 66.7 % had a PD-L1 tumor proportion score (TPS) ≥ 1 % and 45.5 % had a TPS ≥ 50 %. The overall response rate was 33.3 % (95 % confidence interval [CI], 18.0 %–51.8 %), and the disease control rate was 72.7 % (95 % CI, 54.5 %–86.7 %). The median progression-free survival and overall survival were 5.4 (95 % CI, 2.8–9.4) and 15.7 (95 % CI, 11.3–not estimated) months, respectively. PD-L1 expression was not associated with the response or survival outcomes. Patients who achieved disease control exhibited a higher proportion of circulating CD8⁺ T cells (mean, 28.5 % vs. 20.3 %, <em>P</em> = 0.083) and a lower CD4⁺/CD8⁺ ratio (median, 1.4 vs. 1.7, <em>P</em> = 0.048) than did those with progressive disease.</div></div><div><h3>Conclusion</h3><div>Durvalumab-containing combination therapy showed promising efficacy in patients with R/M PSC, irrespective of PD-L1 expression. A lower CD4⁺/CD8⁺ ratio may be associated with favorable disease control.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"213 ","pages":"Article 108916"},"PeriodicalIF":4.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145950220","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":"Amivantamab plus chemotherapy versus chemotherapy for first-line treatment of participants with EGFR exon 20 insertion-mutated advanced non-small cell lung cancer: PAPILLON Asia subgroup analysis","authors":"Caicun Zhou ,&nbsp;Ke-Jing Tang ,&nbsp;Baogang Liu ,&nbsp;Sang-We Kim ,&nbsp;Satoru Kitazono ,&nbsp;Akira Ono ,&nbsp;Muthukkumaran Thiagarajan ,&nbsp;Jen-Yu Hung ,&nbsp;Michael Boyer ,&nbsp;Timuçin Çİl ,&nbsp;Yu Yao ,&nbsp;Rajnish Nagarkar ,&nbsp;John Xie ,&nbsp;Archan Bhattacharya ,&nbsp;Honeylet Wortman-Vayn ,&nbsp;Mahadi Baig ,&nbsp;Trishala Agrawal ,&nbsp;Patricia Lorenzini ,&nbsp;Se-Hoon Lee ,&nbsp;Byoung Chul Cho","doi":"10.1016/j.lungcan.2026.109302","DOIUrl":"10.1016/j.lungcan.2026.109302","url":null,"abstract":"<div><h3>Background</h3><div>Amivantamab is a bispecific, epidermal growth factor receptor (EGFR) and MET-proto-oncogene (MET)-targeting antibody with immune cell-directing activity. In the global Phase 3 PAPILLON trial, amivantamab plus carboplatin-pemetrexed (amivantamab-chemotherapy) significantly improved progression-free survival (PFS) vs chemotherapy alone in previously untreated participants with locally advanced/metastatic NSCLC with <em>EGFR</em> exon 20 insertions (Ex20ins). We evaluated clinical outcomes in Asian participants in PAPILLON (NCT04538664).</div></div><div><h3>Methods</h3><div>Participants were randomized 1:1 to amivantamab-chemotherapy or chemotherapy alone. Study endpoints for this analysis were PFS by blinded independent central review (primary), objective response rate (ORR), duration of response (DoR), PFS after first subsequent therapy (PFS2), overall survival (OS), and safety (secondary). Crossover to amivantamab monotherapy was allowed when disease progressed on chemotherapy alone.</div></div><div><h3>Results</h3><div>Among 186 participants in the Asian sub-cohort, 97 received amivantamab-chemotherapy and 89 received chemotherapy. At median follow-up of 16.6 months, median PFS (95% confidence interval [CI]) in the amivantamab-chemotherapy/chemotherapy groups was 11.5/5.6 months (hazard ratio [HR] 0.34; 95%CI, 0.23–0.49; nominal p &lt; 0.0001) arms. The ORR was 70% vs 51% (odds ratio 2.2, 95%CI, 1.2–3.9; nominal p = 0.012), DoR 10.1 vs 5.5 months. Median PFS2 was not estimable vs 18.8 months (HR 0.46, 95%CI 0.26–0.83; nominal p = 0.008), and median interim OS not estimable vs 24.4 months HR 0.65, 95%CI 0.34–1.24; nominal p = 0.189), respectively, despite substantial (73%) crossover. Safety profiles for both arms were similar to the overall PAPILLON population.</div></div><div><h3>Conclusions</h3><div>Amivantamab-chemotherapy demonstrated superior PFS vs chemotherapy and represents a new standard of care for first-line treatment of Asian participants with Ex20ins-mutated NSCLC.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"213 ","pages":"Article 109302"},"PeriodicalIF":4.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165724","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}