Lung Cancer最新文献

{"title":"Long-term survival with PD-1/PD-L1 inhibitors plus platinum-based chemotherapy versus chemotherapy alone in locally advanced or metastatic pulmonary lymphoepithelioma-like carcinoma: updated follow-up analysis","authors":"Yanna Tang , Wei Du , Xuanye Zhang , Xuan Yang , Yixin Zhou , Sha Fu , Li Zhang , Shaodong Hong","doi":"10.1016/j.lungcan.2025.108855","DOIUrl":"10.1016/j.lungcan.2025.108855","url":null,"abstract":"<div><h3>Purpose</h3><div>Pulmonary lymphoepithelioma-like carcinoma (PLELC), a rare Epstein-Barr virus (EBV)-associated non-small-cell lung cancer (NSCLC) subtype, exhibits distinct clinicopathological features but lacks evidence-based first-line therapy. Our previous study demonstrated superior progression-free survival (PFS) with first-line immunotherapy plus chemotherapy (IO-Chemo) versus chemotherapy alone (Chemo). However, the long-term overall survival (OS) benefit remained uncertain. This study presents the final OS data with extended follow-up.</div></div><div><h3>Methods</h3><div>In this multicenter retrospective study, 133 patients with unresectable stage III–IV PLELC were stratified by first-line therapy: Chemo group (n = 78, platinum-based chemotherapy (PBC)) and IO-Chemo group (n = 55, PBC plus PD-1/PD-L1 inhibitors). The primary analysis in the study was OS.</div></div><div><h3>Results</h3><div>With a median follow-up of 102.6 months (Chemo group) and 48.5 months (IO-Chemo group), IO-Chemo demonstrated improved OS (median not reached vs. 25.6 months; HR 0.48, 95 % CI: 0.30–0.77; <em>P</em> = 0.0023) and PFS (median 15.7 vs. 7.6 months; HR 0.45, 95 % CI: 0.30–0.67; <em>P</em> < 0.0001), compared with chemotherapy alone. Salvage immunotherapy after first-line PBC was associated with prolonged OS compared to no subsequent immunotherapy (median 70.0 vs. 23.6 months, <em>P</em> = 0.0077). Multivariate analysis confirmed Eastern Cooperative Oncology Group (ECOG) performance status 0 (<em>P</em> < 0.001), first-line use of chemoimmunotherapy (<em>P</em> < 0.001) and low baseline EBV DNA levels (<em>P</em> = 0.019) as favorable prognostic factors, while liver metastasis (<em>P</em> < 0.001) and smoking (<em>P</em> = 0.011) were adverse ones.</div></div><div><h3>Conclusion</h3><div>First-line immunotherapy combined with platinum-based chemotherapy is associated with long-term survival benefit in advanced PLELC. These findings support IO-Chemo as the preferred first-line regimen for this rare malignancy.</div><div>Abbreviations: PLELC, Pulmonary lymphoepithelioma-like carcinoma; EBV, Epstein-Barr virus; NSCLC, non-small-cell lung cancer; PFS, progression-free survival; mPFS, median PFS; IO-Chemo, immunotherapy plus chemotherapy; Chemo, chemotherapy; OS, overall survival; mOS, median OS; PBC, platinum-based chemotherapy; PD-1, programmed cell death-1; PD-L1, programmed cell death-ligand 1; EBER-ISH, Epstein-Barr virus-encoded small RNA in situ hybridization; RECIST, Response Evaluation Criteria in Solid Tumors; TP, taxanes (paclitaxel or docetaxel) plus platinum; GP, gemcitabine plus platinum; ECOG PS, Eastern Cooperative Oncology Group performance status; NR, not reached; HR, hazard ratio; CI, confidence interval; ORR, the objective response rate; PR, partial response; SD, stable disease; PD, progressive disease; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; EGFR, epidermal growth factor receptor; AlK, anaplastic lymphoma ","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"211 ","pages":"Article 108855"},"PeriodicalIF":4.4,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145708553","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":"Impact of PD-L1 on first-line osimertinib outcomes in EGFR-mutant NSCLC: real-world data from the AURORA25 study and meta-analysis","authors":"Marliese Alexander ,&nbsp;Malinda Itchins ,&nbsp;Jonathan Felthun ,&nbsp;Adnan Nagrial ,&nbsp;Lauren J. Brown ,&nbsp;Kenneth O’Byrne ,&nbsp;Antony J. Mersiades ,&nbsp;Brett G.M. Hughes ,&nbsp;Lydia Warburton ,&nbsp;Benjamin Y. Kong ,&nbsp;Melissa Moore ,&nbsp;Prunella Blinman ,&nbsp;Samantha Bowyer ,&nbsp;Timothy Clay ,&nbsp;Tim Spelman ,&nbsp;Nick Pavlakis ,&nbsp;Benjamin J. Solomon ,&nbsp;Steven Kao","doi":"10.1016/j.lungcan.2025.108854","DOIUrl":"10.1016/j.lungcan.2025.108854","url":null,"abstract":"<div><h3>Introduction</h3><div>The prognostic significance of PD-L1 expression in <em>EGFR</em>-mutant non-small cell lung cancer (NSCLC) treated with first-line osimertinib remains uncertain. This study evaluated its association with survival in a real-world cohort, supported by meta-analysis.</div></div><div><h3>Materials</h3><div>Retrospective multicentre study using AURORA cohort (ACTRN12625000038493). Primary endpoint was real-world progression-free survival (rwPFS) comparing PD-L1 high (≥50 %) vs low (0–49 %). Secondary endpoints included overall survival (OS), osimertinib duration and response, and analyses at ≥1 %/≥25 %/75 % cut-points. Kaplan-Meier and Cox models were applied. Meta-analysis of studies to 18April2025 reporting first-line osimertinib outcomes by PD-L1 expression was performed.</div></div><div><h3>Results</h3><div>Among 216 patients from 15 centres, median rwPFS was 24.8 months (95 %CI 19.7–29.6). Higher PD-L1 (≥25 %, ≥50 %, ≥75 % versus below each threshold) was associated with shorter rwPFS. The adjusted HR for PD-L1 ≥50 % (n = 35/216, 16 %) vs 0–49 % (n = 181, 84 %) was 3.03 (95 %CI 1.85–4.96, p &lt; 0.001). Median OS was 56.9 months (95 %CI 23.3–57.4): 40.4 with PD-L1 ≥50 and 57.0 with 0–49 %. PD-L1 correlated with shorter OS in unadjusted analyses, with ≥75 % remaining significant after adjustment (HR 2.09, 95 %CI 1.01–4.33, p = 0.046). Meta-analysis of six studies confirmed shorter rwPFS (HR 2.32, 95 %CI 1.16–4.64, p = 0.0178) and OS (HR 2.38, 95 %CI 1.16–4.86, p = 0.0176) for PD-L1 ≥50 % vs 0–49 %.</div></div><div><h3>Conclusions</h3><div>PD-L1 ≥50 % was associated with over twofold risk of progression or death in <em>EGFR</em>-mutant NSCLC on first-line osimertinib. Supported by meta-analysis, results suggest PD-L1 expression is a negative prognostic factor, and these patients may benefit from intensified first-line strategies with prospective evaluation.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"211 ","pages":"Article 108854"},"PeriodicalIF":4.4,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145724457","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":"Patient and oncologist preferences for ALK+ advanced non-small cell lung cancer tyrosine kinase inhibitor treatments: a discrete choice experiment in the United States","authors":"Hannah Le ,&nbsp;Josh Coulter ,&nbsp;Ken Culver ,&nbsp;Joseph C. Cappelleri ,&nbsp;Nada Rifi ,&nbsp;Hui Lu ,&nbsp;Matthew Quaife ,&nbsp;Keila Meginnis ,&nbsp;Gabriela S. Fernandez ,&nbsp;Shailja Vaghela ,&nbsp;Brett Hauber ,&nbsp;Thomas E. Stinchcombe","doi":"10.1016/j.lungcan.2025.108850","DOIUrl":"10.1016/j.lungcan.2025.108850","url":null,"abstract":"<div><h3>Purpose</h3><div>Next-generation anaplastic lymphoma kinase (ALK)-targeting tyrosine kinase inhibitors (TKIs) are standard first-line (1L) treatments for ALK+ advanced non-small cell lung cancer (aNSCLC). Treatments differ in systemic and central nervous system (CNS) efficacy and adverse event (AE) profiles. There is a need for understanding treatment preferences of patients and oncologists in this setting.</div></div><div><h3>Patients and methods</h3><div>Patients receiving TKIs for ALK<em>+</em> aNSCLC and oncologists were recruited from patient databases, patient advocacy groups and an online panel to complete a discrete choice experiment, which included progression-free survival (PFS), brain metastases (BM) development, BM progression, metabolic events, weight gain, CNS AEs, fatigue/asthenia, and muscle/bone pain. Responses were analyzed using a mixed logit model. Relative attribute importance (RAI), minimum acceptable benefit, and maximal acceptable risk were calculated.</div></div><div><h3>Results</h3><div>Of the 151 patients, 23.2 % had BM and 50.3 % were on 1L treatment. Treatment benefits outweighed AEs and contributed to 73.6 % of patients’ and 67.0 % of oncologists’ total RAI. Stopping BM progression was most important to patients (27.2 %), whereas PFS was most important to oncologists (31.1 %). Oncologists placed two and four times as much importance on avoiding CNS AEs and metabolic events, respectively, than patients. Patients placed more importance on avoiding fatigue/asthenia than oncologists.</div></div><div><h3>Conclusions</h3><div>To our knowledge, this was the first study to quantify preferences regarding 1L treatments for ALK+ aNSCLC in the US. As patients and oncologists were shown to have different priorities, understanding the differing trade-offs between treatment benefits and AEs can facilitate shared decision-making and personalized 1L treatment for ALK+ aNSCLC.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"211 ","pages":"Article 108850"},"PeriodicalIF":4.4,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623072","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":"Entrectinib in Asian patients with ROS1 fusion-positive non-small cell lung cancer: updated efficacy and safety analysis","authors":"Shun Lu ,&nbsp;Yun Fan ,&nbsp;Xiaorong Dong ,&nbsp;Yan Yu ,&nbsp;Juan Li ,&nbsp;Jun Zhao ,&nbsp;Chia-Chi Lin ,&nbsp;Pengcheng Zhang ,&nbsp;Yanjun Shi ,&nbsp;Rui Luo ,&nbsp;Xichun Hu","doi":"10.1016/j.lungcan.2025.108851","DOIUrl":"10.1016/j.lungcan.2025.108851","url":null,"abstract":"<div><h3>Background</h3><div>In an integrated analysis of phase I/II trials (STARTRK-2, STARTRK-1, ALKA-372–001), entrectinib induced responses in global populations with advanced <em>ROS1</em>-fusion positive (<em>ROS1</em>-fp) non-small cell lung cancer (NSCLC). This study reports updated efficacy and safety data in Asian patients from the integrated analysis (cutoff: 16 July 2023).</div></div><div><h3>Methods</h3><div>Asian patients with ROS1 tyrosine kinase inhibitor-naïve locally advanced/metastatic <em>ROS1</em>-fp NSCLC, with/without central nervous system (CNS) metastasis were included. The primary endpoints were overall response rate (ORR) and duration of response (DoR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), intracranial (IC)-ORR, IC-DoR, and safety. An exploratory subgroup analysis of patients naïve to systemic therapy in the metastatic setting (1L) was also investigated.</div></div><div><h3>Results</h3><div>The efficacy-evaluable population included 99 patients. Median (range) age was 53 (20, 86) years; 32.3 % of patients had baseline CNS metastases. Confirmed ORR was 68.7 % (95 % confidence interval [CI] 58.6 %–77.6 %); median DoR was 18.6 months (95 % CI 11.1–38.5). Confirmed IC-ORR was 34.8 % (95 % CI 16.4 %–57.3 %); median IC-DoR was 9.4 months (95 % CI 6.8–not evaluable). Median time to CNS progression was 28.9 months (95 % CI 15.7–41.4). In the 1L population (n = 40), confirmed ORR was 67.5 % (95 % CI 50.9 %–81.4 %); median DoR was 38.5 months (95 % CI 11.1–not evaluable). The most frequent treatment-related adverse events were weight increased (45.9 %), constipation (40.4 %), and dysgeusia (39.4 %).</div></div><div><h3>Conclusion</h3><div>This analysis demonstrates continued efficacy of entrectinib in Asian patients with advanced <em>ROS1</em>-fp NSCLC, both overall and in the 1L setting. No new safety signals emerged.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"211 ","pages":"Article 108851"},"PeriodicalIF":4.4,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145668976","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":"KRASG12D/G13D-USP15 axis promotes TGF-β/SMAD signaling and glycolytic flux to accelerate NSCLC pathogenesis","authors":"Ikhlas A. Sindi ,&nbsp;Abdelghafar M. Abu-Elsaoud ,&nbsp;Amany I. Almars ,&nbsp;Nahlah M. Ghouth ,&nbsp;Sameerah Shaheen ,&nbsp;Ahmed M. Basri ,&nbsp;Zaki H Hakami ,&nbsp;Tawfiq N. Jurayb ,&nbsp;Abdullah A. Alqasem ,&nbsp;Iman S. Abumansour ,&nbsp;Hind M. Naffadi ,&nbsp;Nasser A. Elhawary ,&nbsp;Hassan Rudayni ,&nbsp;Mohammed Al-zharani ,&nbsp;Lina M. Alneghery ,&nbsp;Mohamed M.I. Ghoneim","doi":"10.1016/j.lungcan.2025.108848","DOIUrl":"10.1016/j.lungcan.2025.108848","url":null,"abstract":"<div><h3>Background</h3><div>Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related mortality worldwide, with activating <em>KRAS</em> mutations representing a key oncogenic driver. These mutations profoundly reprogram cellular metabolism, especially glycolysis, thereby sustaining uncontrolled tumor proliferation. We identified ubiquitin-specific peptidase 15 (USP15) as a pivotal regulator in KRAS-driven metabolic remodeling and tumor progression. This study aims to elucidate the biological functions and molecular mechanisms of USP15 in <em>KRAS^G12D</em>^/G13D-mutant NSCLC.</div></div><div><h3>Methods</h3><div>Comprehensive bioinformatics analyses were performed to identify key metabolic genes significantly associated with NSCLC prognosis. The expression of USP15 was examined in <em>KRAS</em>-mutant NSCLC tissues and cell lines. Functional assays, including CCK-8, EdU incorporation, wound-healing, and subcutaneous xenograft tumor models, were employed to evaluate the oncogenic role of USP15 <em>in vitro</em> and <em>in vivo</em>. In addition, qPCR, Western blotting, ELISA, immunofluorescence, and Seahorse metabolic flux assays were integrated with transcriptomic and metabolomic profiling to comprehensively delineate the mechanisms by which USP15 regulates tumor metabolism and growth in <em>KRAS^G12D</em>^/G13D-mutant NSCLC.</div></div><div><h3>Results</h3><div><em>USP15</em> expression was elevated in <em>KRAS</em>-mutant NSCLC and was transcriptionally regulated by the MEK/ERK signaling pathway. Silencing <em>USP15</em> significantly inhibited NSCLC cell proliferation, migration, and tumorigenicity, while inducing apoptosis and enhancing chemosensitivity. Multi-omics analyses revealed that USP15 exerts its oncogenic function primarily through modulation of the TGF-β/SMAD signaling axis. Mechanistically, USP15 stabilized SMAD4 by deubiquitination and promoted the phosphorylation of SMAD2/3, thereby sustaining TGF-β/SMAD pathway activation. Moreover, USP15 enhanced glycolytic flux, evidenced by increased extracellular acidification rates and upregulated glycolytic genes expression, ultimately facilitating metabolic adaptation and tumor progression in <em>KRAS^G12D</em>^/G13D-mutant NSCLC.</div></div><div><h3>Conclusion</h3><div>USP15 acts as a critical mediator of oncogenic KRAS-driven metabolic reprogramming in NSCLC by promoting glycolysis via the TGF-β/SMAD signaling cascade. These findings uncover a previously unrecognized role of USP15 in linking metabolic regulation to tumorigenic signaling in <em>KRAS</em>-mutant NSCLC and suggest that targeting USP15 may represent a promising therapeutic strategy for this aggressive cancer subtype.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"211 ","pages":"Article 108848"},"PeriodicalIF":4.4,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623071","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":"First-line treatment in EGFR-mutated non-small cell lung cancer: brief report of an individual patient data comparison of phase 3 clinical trials","authors":"Andrea Torchia ,&nbsp;Arianna Sabatini ,&nbsp;Elisabetta Bengala ,&nbsp;Mattia Alberto Di Civita ,&nbsp;Fabio Ciurluini ,&nbsp;Daniele Marinelli ,&nbsp;Maristella Giammaruco ,&nbsp;Anastasia Laudisi ,&nbsp;Alain Gelibter ,&nbsp;Gabriele Minuti ,&nbsp;Lorenza Landi ,&nbsp;Daniele Santini ,&nbsp;Federico Cappuzzo","doi":"10.1016/j.lungcan.2025.108845","DOIUrl":"10.1016/j.lungcan.2025.108845","url":null,"abstract":"<div><h3>Introduction</h3><div>Clinical trials evaluated the efficacy and safety of novel first-line treatment strategies for advanced epidermal growth factor receptor (<em>EGFR</em>)-mutated non-small cell lung cancer (NSCLC), relative to osimertinib monotherapy.</div></div><div><h3>Methods</h3><div>After review of the literature, we performed an individual patient data comparison of efficacy and safety of investigational regimens from phase 3 randomized controlled trials in untreated <em>EGFR</em>-mutated NSCLC.</div></div><div><h3>Results</h3><div>Two studies were included in the analysis: FLAURA2 and MARIPOSA, evaluating the osimertinib-chemotherapy and amivantamab-lazertinib combinations, respectively. In progression free survival (PFS), there was a statistically significant difference favoring the FLAURA2 in the intent-to-treat (ITT) population [Hazard ratio (HR) 0.79], not confirmed in the overall survival (OS) analysis where we did not find any significant difference. FLAURA2 PFS was longer in patients with central nervous system (CNS) metastases (HR 0.63), without liver metastases (HR 0.73), and with <em>EGFR</em> L858R (HR 0.68). In intracranial PFS (icPFS), there was a statistically significant difference favoring the FLAURA2 (HR 0.52). We found no differences in PFS in patients without CNS metastases, and with exon 19 deletions. No new safety signals resulted from the safety analysis. In FLAURA2, anemia, diarrhea, and neutropenia were more frequent, while in MARIPOSA rash and paronychia.</div></div><div><h3>Conclusion</h3><div>In the ITT population, we found no differences in OS between amivantamab-lazertinib and osimertinib-chemotherapy, despite a slightly higher PFS of the latter. Osimertinib-chemotherapy could be more effective in patients with CNS metastases, without liver metastases, and <em>EGFR</em> L858R mutation, however we could not compare OS in these subgroups. Due to the indirect nature of the comparison and the limitation of the methods our results are not definitive, but rather hypothesis-generating. Other factors must be considered in the choice of the treatment, including patient’s characteristics, the safety profile of the combinations, and center’s facilities and expertise.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108845"},"PeriodicalIF":4.4,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569612","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":"Long-term outcomes of Extensive-Stage small cell lung cancer treated with chemotherapy or Chemo-immunotherapy: A propensity score adjusted cohort study","authors":"Heya Batah ,&nbsp;Emily C. Zabor ,&nbsp;Bridget Adcock ,&nbsp;Monica Lee ,&nbsp;Preeyal Patel ,&nbsp;Meera Patel ,&nbsp;Hadil Zureigat ,&nbsp;Ahmed Nabil Mohamed ,&nbsp;Daniel Paul Nurse ,&nbsp;Yohanna B. Bedelu ,&nbsp;Jacqulyn Tomer ,&nbsp;Lukas Delasos ,&nbsp;Khaled A. Hassan ,&nbsp;Nathan A. Pennell ,&nbsp;Marc A. Shapiro ,&nbsp;James Stevenson ,&nbsp;Alex A. Adjei ,&nbsp;Moaath Khader Mustafa Ali","doi":"10.1016/j.lungcan.2025.108847","DOIUrl":"10.1016/j.lungcan.2025.108847","url":null,"abstract":"<div><h3>Background</h3><div>Combining atezolizumab with carboplatin plus etoposide (Carbo-E) improved overall survival (OS) in patients with extensive-stage small cell lung cancer (ES-SCLC). However, there is a paucity of real-world outcomes. We present the largest and longest follow-up retrospective study evaluating treatment outcomes in ES-SCLC.</div></div><div><h3>Methods</h3><div>We conducted a retrospective cohort study to compare response rate, OS, and progression-free survival (PFS) in patients with ES-SCLC who received Carbo-E, Carbo-E and atezolizumab (Carbo-E-Atezo), and cisplatin and etoposide (Cis-E). We included all adult patients (≥ 18 years) treated at Cleveland Clinic between 1/2010–12/2022. Propensity score (PS) weighting and multivariable Cox proportional hazards regression adjusted for confounders.</div></div><div><h3>Results</h3><div>Among 602 ES-SCLC patients, 375 (62 %) received Carbo-E, 160 (27 %) received Carbo-E-Atezo, and 67 (11 %) received Cis-E. The median age was 67, 65, and 59 years, respectively. The median follow-up among survivors was 23.9 months (IQR: 13.3–––57.3). Five-year unadjusted OS was 4.5 % (Carbo-E), 7 % (Carbo-E-Atezo), and 5.2 % (Cis-E). Carbo-E-Atezo was associated with a longer PS-adjusted median OS than Carbo-E (9.1 vs. 8.2 months, P = 0.039), but no difference was seen in PFS (5.5 vs. 5.5, P = 0.09) or response rate (P &gt; 0.9). Compared to Carbo-E, Cis-E showed higher response rates (OR: 1.67, P = 0.03) but no improvement in OS (11 vs 8.3 months, P = 0.067) or PFS (7.7 vs. 5.5 months, P = 0.058). Cis-E did not differ significantly from Carbo-E-Atezo in response rate, OS, or PFS.</div></div><div><h3>Conclusion</h3><div>Long-term outcomes in ES-SCLC remain poor. Atezolizumab added to Carbo-E modestly improved OS but not PFS. Cisplatin-based regimens increased response rates but did not improve survival.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108847"},"PeriodicalIF":4.4,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145564323","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":"Reappraising preoperative ctDNA in EGFR-mutant NSCLC: from detection to responsible clinical integration","authors":"Man Sun ,&nbsp;Dan Zang ,&nbsp;Jun Chen","doi":"10.1016/j.lungcan.2025.108846","DOIUrl":"10.1016/j.lungcan.2025.108846","url":null,"abstract":"","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108846"},"PeriodicalIF":4.4,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569680","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":"Tarlatamab population survival kinetics in extensive-stage small cell lung cancer: brief report","authors":"David J. Stewart ,&nbsp;Bingnan Zhang ,&nbsp;Razelle Kurzrock","doi":"10.1016/j.lungcan.2025.108844","DOIUrl":"10.1016/j.lungcan.2025.108844","url":null,"abstract":"<div><h3>Purpose</h3><div>Immune checkpoint inhibitors (ICIs) prolong progression-free survival (PFS) and overall survival (OS) in extensive-stage small cell lung cancer (ES-SCLC). ES-SCLC PFS curve exponential decay nonlinear regression analyses (EDNLRAs) suggests that only 10% of patients benefit. Here we report ES-SCLC EDNLRAs for the bispecific T-cell engager tarlatamab.</div></div><div><h3>Experimental design</h3><div>We digitized tarlatamab ES-SCLC PFS and OS curves from published studies and performed EDNLRAs of curve data.</div></div><div><h3>Results</h3><div>All four PFS curves fit 2-phase decay models, suggesting the presence of two distinct subpopulations- one with a short PFS half-life (median 3.2 months, similar to the tarlatamab DeLLphi-304 study chemotherapy arm) and the other with a very long PFS half-life). EDNLRAs indicated that 88 % of the patients belonged to the rapidly progressing subpopulation. The proportion of patients in the subpopulation with long PFS was lower than the study response rates. However, log-linear plots of response-duration curves also suggested 2-phase decay, with one subpopulation having very long responses and the other having very short responses. Two of four OS curves assessed fit 2-phase decay models. Longer follow-up will be required to assess the other two curves. For curves fitting 2-phase decay models, OS half-life for the subpopulation with shorter OS was modestly longer than the OS for the Dellphi-304 chemotherapy arm.</div></div><div><h3>Conclusions</h3><div>In ES-SCLC, EDNLRA of tarlatamab PFS curves and log-linear plots of response duration curves suggest two distinct subpopulations- one deriving marked benefit from tarlatamab and the other deriving much less benefit. Individual patient data might provide insight into underlying driving factors.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108844"},"PeriodicalIF":4.4,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145557126","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":"Prevalence and molecular landscape of NRG1 fusions in Japanese solid tumors: a nationwide data analysis using the C-CAT database","authors":"Masaki Ishida ,&nbsp;Tadaaki Yamada ,&nbsp;Ryo Tsunashima ,&nbsp;Midori Morita ,&nbsp;Nobutaka Kataoka ,&nbsp;Yusuke Kunimatsu ,&nbsp;Ryo Sawada ,&nbsp;Tae Hata ,&nbsp;Hayato Kawachi ,&nbsp;Masahiro Iwasaku ,&nbsp;Yasuto Naoi ,&nbsp;Koichi Takayama","doi":"10.1016/j.lungcan.2025.108843","DOIUrl":"10.1016/j.lungcan.2025.108843","url":null,"abstract":"<div><h3>Introduction</h3><div>Neuregulin 1 (<em>NRG1</em>) gene fusions are critical oncogenic drivers that activate the ERBB signaling pathway across various solid tumors. Although targeted therapies for <em>NRG1</em> fusion-positive cancers are advancing rapidly in clinical settings, their epidemiological and clinicogenomic characteristics remain poorly understood, warranting large-scale investigations.</div></div><div><h3>Methods</h3><div>We performed a retrospective analysis of patients with advanced solid tumors who were registered in the Center for Cancer Genomics and Advanced Therapeutics database of Japan between June 2019 and February 2025. Our evaluation focused on the prevalence of <em>NRG1</em> fusions, identities of fusion partners, co-occurring genomic alterations, tumor mutational burden, microsatellite instability status, and relevant clinical characteristics.</div></div><div><h3>Results</h3><div>Our study included 95,149 patients with advanced solid tumors who underwent comprehensive genomic profiling. Among them, 29 (0.03 %) harbored <em>NRG1</em> fusions, most frequently in lung cancer (17 of 5,670 cases, 0.30 %). CD74 emerged as the predominant fusion partner, constituting 82.4 % of lung cancers, whereas other solid tumors exhibited a more diverse range of partners. Co-occurring genomic alterations were detected in 20 of 29 patients (69.0 %), with the most frequent alterations found in <em>CDKN2A</em>, <em>CDKN2B</em>, and <em>MTAP</em>. Additionally, pathological examination revealed mucinous adenocarcinoma in 17.6 % of lung cancers associated with <em>NRG1</em> fusions.</div></div><div><h3>Conclusion</h3><div>This study confirms that <em>NRG1</em> fusions are rare but significantly associated with lung cancer and the CD74 fusion partner. Our nationwide analysis represents the most comprehensive assessment of <em>NRG1</em> fusions in Japanese patients with advanced solid tumors.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108843"},"PeriodicalIF":4.4,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534535","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}