Clinical lung cancer最新文献

{"title":"ENTRÉE Lung Platform Trial Sub-study 1: Phase II Randomized Efficacy and Safety Analysis of Feladilimab Plus Docetaxel Versus Docetaxel Monotherapy in Advanced/Recurrent NSCLC","authors":"Marina Chiara Garassino,&nbsp;Sophie Cousin,&nbsp;Benjamin Besse,&nbsp;Adrian Sacher,&nbsp;Sergey Orlov,&nbsp;Michael Schenker,&nbsp;Enriqueta Felip,&nbsp;Oleg Gladkov,&nbsp;Cristina H. Messina,&nbsp;Antara Majumdar,&nbsp;Zhenhua Jeremy Wu,&nbsp;Natalie O. Karpinich,&nbsp;Steven Hirschfeld,&nbsp;Marc Ballas,&nbsp;Martin Reck","doi":"10.1016/j.cllc.2026.04.003","DOIUrl":"10.1016/j.cllc.2026.04.003","url":null,"abstract":"<div><h3>Background</h3><div>Combining treatments with different mechanisms may improve immunosurveillance and outcomes in advanced/recurrent non–small cell lung cancer (NSCLC) after immunotherapy. ENTRÉE Lung (NCT03739710) is a phase 2, open-label platform trial utilizing a master protocol to investigate novel regimens versus standard of care (SoC) in separate sub-studies. Sub-study 1 investigated the immunoglobulin G4 inducible T-cell costimulator agonist antibody, feladilimab, plus docetaxel versus SoC, docetaxel monotherapy.</div></div><div><h3>Patients and methods</h3><div>Patients with advanced/recurrent NSCLC who progressed on prior anti-programmed cell death (ligand)-1 and platinum-based combination chemotherapies were randomized to feladilimab (80 mg) plus docetaxel 75 mg/m² (both intravenous) or docetaxel 75 mg/m² every 3 weeks until progressive disease/unacceptable toxicity. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), tumor response (including overall response rate [ORR]), and safety. Exploratory endpoints included biomarkers.</div></div><div><h3>Results</h3><div>A total of 105 patients were randomized to feladilimab plus docetaxel (<em>n</em> = 70) or docetaxel (<em>n</em> = 35). Median OS was 7.8 months with feladilimab plus docetaxel versus 8.2 months with docetaxel; hazard ratio (HR) 1.5 (95% confidence interval [CI], 0.92, 2.44). Median PFS for feladilimab plus docetaxel versus docetaxel was 3.4 months versus 3.3 months, and ORR was 19% versus 11%; HR 0.84 (95% CI, 0.54, 1.32). Most frequently reported treatment-related adverse events included anemia (34% vs. 24%), nausea (34% vs. 15%), alopecia (27% vs. 21%), and asthenia (27% vs. 18%).</div></div><div><h3>Conclusion</h3><div>Feladilimab plus docetaxel has an acceptable safety profile in the second-line treatment of advanced/recurrent NSCLC. No survival outcomes or tumor response advantages were observed with the addition of feladilimab to docetaxel in this setting.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 5","pages":"Pages 65-76.e2"},"PeriodicalIF":3.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147927332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Immune Checkpoint Inhibitor-Combined Chemotherapy as First-Line Treatment for Non-Small Cell Lung Cancer With Brain Metastases","authors":"Amira Aliouat ,&nbsp;Agathe Chareire ,&nbsp;Teo Bodergat ,&nbsp;Coralie Moncharmont ,&nbsp;Clémence Pierre ,&nbsp;Margaux Geier ,&nbsp;Julie Lasvergnas ,&nbsp;Maëva Zysman ,&nbsp;Julian Pinsolle ,&nbsp;Cyril Guibert ,&nbsp;Emilie Perrot ,&nbsp;Anton Tekhneriadov ,&nbsp;Elvire Pons-Tostivint ,&nbsp;Anne-Claire Toffart","doi":"10.1016/j.cllc.2026.04.008","DOIUrl":"10.1016/j.cllc.2026.04.008","url":null,"abstract":"<div><div>Immune checkpoint inhibitor-combined chemotherapy (chemo-ICI) is a cornerstone treatment for metastatic non-small cell lung cancer (NSCLC) without oncogenic addictions. However, immunotherapy’s efficacy in patients with brain metastases remains unclear. This multicenter retrospective study assessed NSCLC patients with brain metastases who received first-line chemo-ICI between January 2020 and December 2022. The primary outcome was the 12-week intracranial control (IC) rate. Progression-free survival (PFS), overall survival (OS), and neurological tolerance were also evaluated. Of 338 patients from 11 French hospitals, most were male (n = 196, 58%), with a median age of 60 (IQR 54-66) years, and an ECOG performance status (ECOG-PS) of 0 or 1 in 267 (79%) patients. Most (n = 291, 86%) had adenocarcinoma, and 130 (38.6%) had programmed death-ligand 1 (PD-L1) expression &lt;1%. At diagnosis, 174 (51.5%) received steroids. Sixty-six (19.8%) underwent prior brain radiotherapy. Of 240 evaluable patients, the 12-week ICC rate was 74.2%. Median OS and PFS were 22.1 (95% CI 16.5-29.3) and 7.3 months (95% CI 5.9-8.5), respectively. Variables independently associated with CNS progression were ECOG-PS &gt;1 (vs. 0; OR 12.15; 95% CI 3.93-37.54) and extracerebral metastases (OR 3.52; 95% CI 1.55-7.99). Conversely, high PD-L1 expression (≥50%) (vs. 0; OR 0.41; 95% CI 0.19-0.90) and prior brain radiotherapy (OR 0.25; 95% CI 0.10-0.68) were associated with better ICC. No new toxicity was observed. Chemo-ICI was effective and safe in NSCLC patients with CNS metastases, including corticosteroid-treated symptomatic patients. High PD-L1 expression and early brain radiotherapy were favorable prognostic factors.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 5","pages":"Pages 42-47"},"PeriodicalIF":3.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148053165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brief Report: Treatment Patterns and Outcomes in a Large Real-World Cohort of Patients With ES-SCLC Treated With First-Line Chemoimmunotherapy in the United States","authors":"Xiuning Le ,&nbsp;Elizabeth Serra ,&nbsp;Kaitlyn Easson ,&nbsp;Remi Bellefleur ,&nbsp;Patrick Gagnon-Sanschagrin ,&nbsp;Annie Guérin ,&nbsp;Soetkin Vlassak ,&nbsp;Aaron Samson ,&nbsp;Victoria Guan ,&nbsp;Ankur A. Dashputre","doi":"10.1016/j.cllc.2026.02.004","DOIUrl":"10.1016/j.cllc.2026.02.004","url":null,"abstract":"<div><h3>Introduction</h3><div>Chemoimmunotherapy with atezolizumab or durvalumab has been the standard-of-care first-line (1L) treatment for extensive-stage small cell lung cancer (ES-SCLC) in the United States (US) since 2019. However, real-world evidence on treatment patterns, progression-free survival (rwPFS), and overall survival (rwOS) in this era is lacking.</div></div><div><h3>Methods</h3><div>This retrospective study identified patients with ES-SCLC treated with 1L chemoimmunotherapy from a claims database in the US (Komodo Research Data; 03/2018-09/2023); treatment patterns were described from diagnosis by line of therapy. rwPFS and rwOS were assessed from 1L chemoimmunotherapy initiation using the Kaplan-Meier estimator. Mortality risk factors were assessed using a multivariable Cox proportional hazards model.</div></div><div><h3>Results</h3><div>A total of 2,788 patients with ES-SCLC receiving 1L chemoimmunotherapy were identified (median age 65 years, 49.5% female); 89.5% received atezolizumab-based and 10.5% received durvalumab-based 1L chemoimmunotherapy. One-third (33.2%) of patients received a second-line regimen, and 10.3% received a third-line regimen. Among patients with sufficient follow-up, median rwPFS and rwOS from 1L chemoimmunotherapy was 4.2 (95% CI: 4.0-4.4) months and 10.8 (95% CI: 10.3-11.3) months, respectively. Risk factors significantly associated with increased mortality included older age (≥75 years), male sex, comorbidities (cardiovascular, renal, and chronic obstructive pulmonary diseases), and distant metastases (liver, brain, bone, adrenal gland).</div></div><div><h3>Conclusions</h3><div>In real-world clinical practice, patients with ES-SCLC treated with 1L chemoimmunotherapy experience rapid disease progression and death and infrequently receive subsequent treatment. Prognosis is particularly poor among older patients and those with comorbidities or distant metastases. These findings underscore a need for effective treatment options in 1L and beyond.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 4","pages":"Pages 41-46.e3"},"PeriodicalIF":3.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Clinical Outcomes of Concurrent Chemotherapy and Dose-Escalated Twice-Daily Radiotherapy With Simultaneous Integrated Boost (SIB) for Limited-Stage Small Cell Lung Cancer","authors":"Sukran Celikarslan ,&nbsp;Duygu Sezen ,&nbsp;Merve Duman ,&nbsp;Nulifer Kilic Durankus ,&nbsp;Saliha Ezgi Oymak ,&nbsp;Caglayan Selenge Beduk Esen ,&nbsp;Aladin Rustamov ,&nbsp;Abdullah Nasir ,&nbsp;Sena Birsen Guclu ,&nbsp;Metin Kanıtez ,&nbsp;Kerim Kaban ,&nbsp;Fulden Yumuk ,&nbsp;Fatih Selcukbiricik ,&nbsp;Nil Molinas Mandel ,&nbsp;Ezgi Cesur ,&nbsp;Suat Erus ,&nbsp;Serhan Tanju ,&nbsp;Sukru Dilege ,&nbsp;Terman Gumus ,&nbsp;Cetin Atasoy ,&nbsp;Ugur Selek","doi":"10.1016/j.cllc.2026.03.010","DOIUrl":"10.1016/j.cllc.2026.03.010","url":null,"abstract":"<div><h3>Introduction</h3><div>The standard concurrent chemoradiotherapy (c-CT) regimen for limited-stage small cell lung cancer (LS-SCLC) has historically been 45 Gy in 30 twice-daily (BID) fractions. Recent findings by Yu et al. suggest that dose escalation up to 54 Gy may improve overall survival (OS) without increasing toxicity. However, real-world evidence on the safety and efficacy of dose escalation using modern radiotherapy techniques remains limited. This study aimed to evaluate survival outcomes and treatment tolerability in LS-SCLC patients treated with dose-escalated BID radiotherapy using the simultaneous integrated boost (SIB) technique.</div></div><div><h3>Materials and Methods</h3><div>Patients with LS-SCLC who received c-CT and BID radiotherapy with SIB-based dose escalation (54Gy/30fr) were retrospectively analyzed. All treatment planning was performed with Intensity-Modulated Radition Therapy using heterogeneity correction after 4D-CT simulation. The primary endpoint was OS; secondary endpoints included disease-free survival (DFS) and treatment-related toxicities.</div></div><div><h3>Results</h3><div>From March 2010 to December 2024, 66 patients were included. Median age was 65 years, with a median follow-up of 31 months. Median OS was 53 months and median DFS 18 months. Grade 3 acute esophagitis occurred in 7.6%, and grade 3 pneumonitis in 3%. No grade ≥4 toxicities were observed. No grade ≥4 toxicities were reported.</div></div><div><h3>Conclusion</h3><div>Dose-escalated BID radiotherapy using SIB was effective and well tolerated, yielding favorable local control. However, distant metastases remained the predominant failure pattern, limiting the OS benefit compared with the 62.4 months reported by Yu et al. Interpretation should consider the retrospective design, treatment heterogeneity over a decade, and potential selection biases.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 4","pages":"Pages 123-131.e2"},"PeriodicalIF":3.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Retrospective, Multicenter Analysis Within the National Network Genomic Medicine Lung Cancer in Germany to Detect RET Fusions as a Possible Mechanism of Resistance in Patients With EGFR Mutations","authors":"Cornelia Kropf-Sanchen ,&nbsp;Nikolaj Frost ,&nbsp;Jonas Kuon ,&nbsp;Martin Wermke ,&nbsp;Stefan Krüger ,&nbsp;Florian Fuchs ,&nbsp;Marcel Wiesweg ,&nbsp;Petros Christopoulos ,&nbsp;Michael Thomas ,&nbsp;Nadine T. Gaisa ,&nbsp;Michael Josten ,&nbsp;Carina Wenzel ,&nbsp;Jan Buth ,&nbsp;Florian Glanemann ,&nbsp;Albrecht Stenzinger ,&nbsp;Matthias F. Froelich ,&nbsp;Melanie Janning ,&nbsp;Maike Colienne ,&nbsp;Verena Haselmann ,&nbsp;Sonja Loges","doi":"10.1016/j.cllc.2026.03.005","DOIUrl":"10.1016/j.cllc.2026.03.005","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Resistance to third-generation EGFR tyrosine kinase inhibitors (TKIs) such as osimertinib remains a major challenge in the treatment of &lt;em&gt;EGFR&lt;/em&gt;-mutated non-small cell lung cancer (NSCLC). While on-target and bypass mechanisms such as &lt;em&gt;MET&lt;/em&gt; amplification are well-characterized, oncogenic fusions—particularly &lt;em&gt;RET&lt;/em&gt; fusions—are emerging as relevant resistance mechanisms in a subset of patients. The feasibility of dual inhibition strategies and personalized monitoring through liquid biopsy remains underexplored in real-world clinical practice.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and Methods&lt;/h3&gt;&lt;div&gt;This retrospective, multicenter study within the German national Network Genomic Medicine (nNGM) Lung Cancer identified patients with advanced &lt;em&gt;EGFR&lt;/em&gt;-mutated NSCLC and co-occurring &lt;em&gt;RET&lt;/em&gt; fusions between 2018 and 2024. Clinicopathological data, treatment history, progression-free survival (PFS), and overall survival (OS) were analyzed. &lt;em&gt;RET&lt;/em&gt; alterations were either present at diagnosis or acquired under EGFR-TKI therapy. In 2 patients, a personalized droplet digital PCR (ddPCR) assay was developed to monitor &lt;em&gt;EGFR&lt;/em&gt; and &lt;em&gt;RET&lt;/em&gt; alterations longitudinally using liquid biopsy.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Nine patients met the inclusion criteria (median age: 54 years). RET fusions were detected at diagnosis in 2 patients and acquired in 7 patients during EGFR-TKI treatment, with a median time to detection of 11.4 months. &lt;em&gt;RET&lt;/em&gt; fusion partners included &lt;em&gt;CCDC6&lt;/em&gt; (&lt;em&gt;n&lt;/em&gt; = 4), &lt;em&gt;KIF5B&lt;/em&gt; (&lt;em&gt;n&lt;/em&gt; = 2), &lt;em&gt;NCOA4&lt;/em&gt; (&lt;em&gt;n&lt;/em&gt; = 2), and one case with an unknown partner. The most common EGFR mutation was exon 19 deletion (&lt;em&gt;n&lt;/em&gt; = 6), followed by L858R mutation (&lt;em&gt;n&lt;/em&gt; = 1), with 2 patients harboring exon 20 insertions. First-line treatment consisted of RET inhibition with pralsetinib in the 2 patients with atypical EGFR mutations, third-generation EGFR-TKIs in 6 patients (median PFS: 13.5 ± 9.2 months), and a second-generation EGFR-TKI (afatinib) in one patient (PFS: 8.7 months). Following progression, all patients underwent re-biopsy, confirming persistence of the &lt;em&gt;EGFR&lt;/em&gt; mutation and presence of &lt;em&gt;RET&lt;/em&gt; fusions. Second-line therapies varied, including chemo-immunotherapy (&lt;em&gt;n&lt;/em&gt; = 4, mPFS: 6.5 ± 2.5 months), chemotherapy (&lt;em&gt;n&lt;/em&gt; = 1, PFS: 0.3 months), and best supportive care (&lt;em&gt;n&lt;/em&gt; = 1). Three patients received the combined EGFR-TKI osimertinib and RET-TKI pralsetinib either in second- or third-line, with PFS ranging from 3.9 to 10.5 months. Median OS for the cohort was 27 months (range: 7 to &gt;30 months), with 4 patients still alive at last follow-up. In 2 patients, a personalized ddPCR assay enabled non-invasive, longitudinal monitoring of &lt;em&gt;EGFR&lt;/em&gt; and &lt;em&gt;RET&lt;/em&gt; alterations, closely reflecting the clinical course of disease. In 1 patient, molecular recurrence in liquid biopsy preceded clinical and radiologic","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 4","pages":"Pages 97-107.e1"},"PeriodicalIF":3.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"To Stop or Not to Stop: Is It Time to Reevaluate Immunotherapy Duration in Advanced/Metastatic NSCLC?","authors":"Matthew Lee ,&nbsp;Shuai Wang ,&nbsp;Lova Sun ,&nbsp;Balazs Halmos","doi":"10.1016/j.cllc.2026.03.012","DOIUrl":"10.1016/j.cllc.2026.03.012","url":null,"abstract":"<div><div>Immunotherapy has transformed the treatment landscape of advanced and metastatic non–small cell lung cancer, providing durable survival benefits for a subset of patients. Despite widespread adoption of immune checkpoint inhibitors as frontline therapy, the optimal duration of treatment remains uncertain. Current practice often limits therapy to 2 years or continues indefinitely until progression based on landmark clinical trials that arbitrarily chose these timepoints, and it is not biologically based. Unfortunately, there is still limited prospective or clinical trial evidence to guide such decisions. Retrospective studies have suggested that discontinuation at 2 years may not compromise outcomes, but also raise concerns about balancing efficacy with cumulative toxicities and financial burden. This review provides updated data and ongoing trials seeking to answer these questions, along with potential emerging biomarkers, including circulating tumor DNA (ctDNA) and imaging with positron emission tomography/computed tomography that can help risk-stratify and guide and refine treatment strategies.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 4","pages":"Pages 29-40"},"PeriodicalIF":3.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147799548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brief Report: A Pilot Study Evaluating the Feasibility, Safety, and Compliance With a Fasting-Mimicking Diet in Patients With Metastatic Non–Small Cell Lung Cancer","authors":"Fatima Ghaddar ,&nbsp;Shahid Ahmed ,&nbsp;Beth Kirsch ,&nbsp;Laura Jennewein ,&nbsp;Margaret M. Uhrich ,&nbsp;Sandra K. Althouse ,&nbsp;Valter Longo ,&nbsp;Shadia Jalal","doi":"10.1016/j.cllc.2026.03.017","DOIUrl":"10.1016/j.cllc.2026.03.017","url":null,"abstract":"<div><h3>Introduction</h3><div>The fasting-mimicking diet (FMD) is a plant-based, calorie-restricted, low-carbohydrate, low-protein, 4- or 5-day diet that reproduces short-term fasting physiology and promotes synergy with cancer therapies. Despite established safety and feasibility, FMD data in advanced lung cancer remain lacking.</div></div><div><h3>Materials and Methods</h3><div>This open-label, single-arm, single-center pilot study recruited metastatic non–small cell lung cancer (NSCLC) adult patients (Body mass index &gt;18, Eastern Cooperative Oncology Group performance status [PS] 0-2) who were clinically stable on first-line therapy for ≥2 months. Patients received one 4-day FMD. Primary outcomes were feasibility (proportion completing FMD), safety (proportion completing FMD without grade 3-4 adverse events), and compliance with FMD caloric requirements. Weight and biologic measures—complete blood counts and metabolic panels—were obtained at baseline and 21 or 28 days post-FMD. Weight was also measured during FMD. The secondary outcome was self-reported willingness to repeat FMD.</div></div><div><h3>Results</h3><div>Ten participants initiated FMD. Median age was 57.2 years (40.5, 76.2), median baseline Body mass index 28.1 (22.6, 37.5), and baseline Eastern Cooperative Oncology Group PS 0-1. Most patients were female (70%), had adenocarcinoma (90%), and received oral targeted therapy (80%). Fifty percent were White/Caucasian, 30% Black/African American, and 20% Asian. Ninety percent completed FMD. No grade 3 to 4 adverse events occurred. Most common side effects were grades 1 to 2—nausea (30%), abdominal pain (20%), fatigue (20%), headache (20%). Weight loss remained &lt; 10% from baseline. Biologic markers were normal. Compliance rate was 70% (95% CI, 34.8-93.3). Eighty percent of patients expressed willingness to repeat FMD.</div></div><div><h3>Conclusion</h3><div>A single FMD cycle is safe and feasible in relatively young, advanced NSCLC patients on oral targeted therapy.</div></div><div><h3>Clinical Trial Information</h3><div>ClinicalTrials.gov Identifier: NCT03700437.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 4","pages":"Pages 24-28"},"PeriodicalIF":3.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147799549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frequent RBM10 Comutation and a Mutually Exclusive Relationship With Other TP53 Pathway Aberrations in Early-Stage Non–Small-Cell Lung Cancer with EGFR Mutation","authors":"Kenichi Suda ,&nbsp;Kazuko Sakai ,&nbsp;Masaoki Ito ,&nbsp;Hana Oiki ,&nbsp;Shota Fukuda ,&nbsp;Shuta Ohara ,&nbsp;Akira Hamada ,&nbsp;Masato Chiba ,&nbsp;Masaki Shimoji ,&nbsp;Kazuto Nishio ,&nbsp;Yasuhiro Tsutani","doi":"10.1016/j.cllc.2026.03.002","DOIUrl":"10.1016/j.cllc.2026.03.002","url":null,"abstract":"<div><h3>Background</h3><div>RNA-binding motif 10 (<em>RBM10</em>) mutation in non–small-cell lung cancer (NSCLC) is associated with decreased sensitivity to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors in vitro and in patients who received osimertinib as neoadjuvant treatment or palliative systemic therapy. The incidence of this mutation in early-stage NSCLC and the relationship with other mutations are unknown.</div></div><div><h3>Materials and methods</h3><div>We analyzed the clinical and genomic data of 190 patients with NSCLC who underwent surgical resection between June 2022 and April 2024. Genomic data were obtained from whole-exome sequencing performed in an ongoing multicenter prospective observational study.</div></div><div><h3>Results</h3><div><em>RBM10</em> mutation was detected in 17 of 152 patients with nonsquamous NSCLC (11%) and not detected in 38 patients with squamous cell carcinomas. The incidences of <em>RBM10</em> mutation were higher in tumors with <em>EGFR</em> mutation (21%) and tumors with <em>KRAS</em> mutation (12%) compared with those without <em>EGFR</em>/<em>KRAS</em> mutations (2%, <em>P</em> &lt; .001 and <em>P</em> = .07, respectively). In tumors with <em>EGFR</em> mutation (<em>N</em> = 68), <em>RBM10</em> mutation was significantly associated with age (&gt; 76 years, <em>P</em> &lt; .01), the presence of ground-glass opacity (<em>P</em> &lt; 0.05), and histological grade 1 (<em>P</em> &lt; .05). We observed mutually exclusive relationships between <em>RBM10</em> mutation, <em>TP53</em> mutation, and <em>MDM2</em> gene amplification, and a high incidence of <em>RBM10</em> mutation or <em>MDM2</em> gene amplification in tumors with EGFR L858R mutation/uncommon mutation.</div></div><div><h3>Conclusion</h3><div><em>RBM10</em> mutation is frequent in Japanese patients with NSCLC with <em>EGFR</em> mutation, especially those with L858R or uncommon mutations, and was associated with late-onset and features of indolent tumor growth.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 4","pages":"Pages 73-80.e3"},"PeriodicalIF":3.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147615847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Consolidation Durvalumab on Local Control Following Chemoradiotherapy for Non–Small Cell Lung Cancer","authors":"Adel Zakharia,&nbsp;William Bodner,&nbsp;Balazs Halmos,&nbsp;Madhur Garg,&nbsp;Rasim Gucalp,&nbsp;Haiying Cheng,&nbsp;Brendon Stiles,&nbsp;Nitin Ohri","doi":"10.1016/j.cllc.2026.03.004","DOIUrl":"10.1016/j.cllc.2026.03.004","url":null,"abstract":"<div><h3>Background</h3><div>The PACIFIC trial demonstrated that durvalumab after concurrent chemoradiotherapy (CCRT) improves survival in locally advanced non–small cell lung cancer (NSCLC), but its impact on in-field local control is unclear. We reviewed outcomes with and without consolidation durvalumab to evaluate its effect on local control of treated tumors and lymph nodes.</div></div><div><h3>Patients and Methods</h3><div>We reviewed patients with locally advanced NSCLC who underwent staging FDG-PET and CCRT with or without consolidation durvalumab between 2007 and 2023. Patients with progression or death within 6 weeks postradiotherapy were excluded. Lesions were categorized as high- or low-risk using a volume cutoff of 25 cc. Kaplan–Meier and competing risks analyses were used to evaluate progression-free survival (PFS), overall survival (OS), and local progression. Tumor control probability (TCP) modeling was performed to characterize the association between lesion volume and local control.</div></div><div><h3>Results</h3><div>Among 233 patients with 696 irradiated lesions, 88 patients (38%) received durvalumab. Median follow-up was 70 months overall and 44 months with durvalumab. Durvalumab receipt was associated with improved PFS (median 16 vs. 11 months, <em>P</em> = .011) and improved OS (median 50 vs. 30 months, <em>P</em> = .042). Durvalumab was not significantly associated with local recurrence rate on a patient level (2-year recurrence rate 12% vs. 17%, <em>P</em> = .361). At the lesion level, the 2-year recurrence rate was 6% overall, and high-risk lesions had greater recurrence risk (19% vs. 2%, <em>P</em> &lt; .001).</div></div><div><h3>Conclusions</h3><div>Many patients with LA-NSCLC have little risk of in-field recurrence after chemoradiotherapy, with or without consolidation durvalumab. Bulky lesions remain prone to failure, highlighting the need for improved local control strategies in high-risk disease.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 4","pages":"Pages 91-96"},"PeriodicalIF":3.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147638116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Programmed Death Ligand 1 Expression on Outcomes in Stage I-II Epidermal Growth Factor Receptor-Mutant Lung Adenocarcinoma","authors":"Kotaro Murakami ,&nbsp;Yoshihisa Shimada ,&nbsp;Masatsugu Hamaji ,&nbsp;Keiji Yamanashi ,&nbsp;Yohei Kawaguchi ,&nbsp;Yujin Kudo ,&nbsp;Hidenao Kayawake ,&nbsp;Yojiro Yutaka ,&nbsp;Hiroshi Date ,&nbsp;Norihiko Ikeda","doi":"10.1016/j.cllc.2026.03.013","DOIUrl":"10.1016/j.cllc.2026.03.013","url":null,"abstract":"<div><h3>Background</h3><div>We aimed to investigate the clinicopathological characteristics and prognostic significance of programmed death ligand 1 (PD-L1) expression in patients with pathological stage I–II epidermal growth factor receptor (<em>EGFR</em>)-mutant lung adenocarcinoma (LUAD) undergoing surgical resection.</div></div><div><h3>Patients and Methods</h3><div>Patients with <em>EGFR</em>-mutant LUAD who underwent complete surgical resection between 2017 and 2019 at 2 institutions were retrospectively analyzed. PD-L1 expression was assessed using the tumor proportion score (TPS) with a cutoff of ≥ 1%. Clinical outcomes, including recurrence-free survival (RFS) and overall survival, were examined based on PD-L1 expression. Propensity score matching was used to reduce confounding, and multivariate analyses were performed to identify independent prognostic factors. Additionally, progression-free survival (PFS) was assessed based on PD-L1 expression to investigate the efficacy of EGFR-tyrosine kinase inhibitors (EGFR-TKIs) after postoperative recurrence.</div></div><div><h3>Results</h3><div>Among 243 patients identified, those classified as PD-L1-positive (TPS ≥ 1%) exhibited significantly shorter 5-year RFS than PD-L1-negative patients (81.3% vs. 95.3%, <em>P</em> &lt; .001). Male sex, advanced pathological T factor, tumor differentiation, and visceral pleural invasion or lymphovascular invasion were identified as significant predictors of recurrence. Although the population was small, the PFS for PD-L1-positive patients who received EGFR-TKIs was 21.4 months, which was significantly longer than the 7.6 months for PD-L1-negative patients.</div></div><div><h3>Conclusions</h3><div>PD-L1 expression is a useful biomarker for predicting postoperative recurrence in patients with <em>EGFR-</em>mutant LUAD, and the therapeutic effect of EGFR-TKIs is sufficient even in PD-L1-positive patients. These findings support the current treatment guidelines and highlight the need for further studies to explore the role of PD-L1 in postoperative management.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 4","pages":"Pages 141-148.e4"},"PeriodicalIF":3.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}