Pub Date : 2026-01-11DOI: 10.1016/j.cllc.2026.01.003
Anson Man Lok Yeung, James Chung Hang Chow
Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is an uncommon and aggressive malignancy, accounting for approximately 3% of all primary lung malignancies. Due to its rarity, the treatment paradigm for LCNEC is primarily derived from retrospective data from non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). This review synthesizes current evidence and discusses emerging treatment strategies. For medically fit patients with resectable disease, surgical resection, in particular lobectomy, should be offered, while stereotactic body radiation therapy can be reserved for medically inoperable patients. Adjuvant chemotherapy is suggested for most resected tumors, with SCLC regimens (eg, etoposide-cisplatin) associated with better outcomes; however, very early-stage tumors (stage IA) warrant individualized decision-making. There is currently no evidence supporting the use of adjuvant immunotherapy in LCNEC. The role of adjuvant radiotherapy, neoadjuvant therapy and prophylactic cranial irradiation in LCNEC remains undefined. For unresectable, locally advanced disease, concurrent chemoradiation with etoposide-cisplatin followed by consolidation durvalumab is recommended, although the optimal dose-fractionation and the duration of consolidation immunotherapy remain to be investigated. In metastatic disease, etoposide-platinum chemotherapy remains the first-line treatment, while targeted therapy can be considered if tumors harbor actionable genomic alterations. The potential benefit of immunotherapy is currently under investigation. While several second-line treatment options have been reported with modest efficacy, local ablative treatment has shown promise in oligometastatic LCNEC. Among the most promising emerging treatment strategies are DLL3-targeting therapies, buoyed by the recent success of tarlatamab in SCLC. The evolving role of molecular profiling in prognostication and treatment decision-making is also examined.
{"title":"Management of Pulmonary Large-Cell Neuroendocrine Carcinoma (LCNEC): An Updated Review.","authors":"Anson Man Lok Yeung, James Chung Hang Chow","doi":"10.1016/j.cllc.2026.01.003","DOIUrl":"https://doi.org/10.1016/j.cllc.2026.01.003","url":null,"abstract":"<p><p>Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is an uncommon and aggressive malignancy, accounting for approximately 3% of all primary lung malignancies. Due to its rarity, the treatment paradigm for LCNEC is primarily derived from retrospective data from non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). This review synthesizes current evidence and discusses emerging treatment strategies. For medically fit patients with resectable disease, surgical resection, in particular lobectomy, should be offered, while stereotactic body radiation therapy can be reserved for medically inoperable patients. Adjuvant chemotherapy is suggested for most resected tumors, with SCLC regimens (eg, etoposide-cisplatin) associated with better outcomes; however, very early-stage tumors (stage IA) warrant individualized decision-making. There is currently no evidence supporting the use of adjuvant immunotherapy in LCNEC. The role of adjuvant radiotherapy, neoadjuvant therapy and prophylactic cranial irradiation in LCNEC remains undefined. For unresectable, locally advanced disease, concurrent chemoradiation with etoposide-cisplatin followed by consolidation durvalumab is recommended, although the optimal dose-fractionation and the duration of consolidation immunotherapy remain to be investigated. In metastatic disease, etoposide-platinum chemotherapy remains the first-line treatment, while targeted therapy can be considered if tumors harbor actionable genomic alterations. The potential benefit of immunotherapy is currently under investigation. While several second-line treatment options have been reported with modest efficacy, local ablative treatment has shown promise in oligometastatic LCNEC. Among the most promising emerging treatment strategies are DLL3-targeting therapies, buoyed by the recent success of tarlatamab in SCLC. The evolving role of molecular profiling in prognostication and treatment decision-making is also examined.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 2","pages":"85-97"},"PeriodicalIF":3.3,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137181","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}
ROS1 fusions are rare in lung squamous cell carcinoma (SCC), but they can occur, especially in non-smoking patients, highlighting the importance of comprehensive molecular testing even in SCC histology.
•
Repotrectinib, a next-generation ROS1 tyrosine kinase inhibitor, demonstrated marked tumor regression and good tolerability as first-line treatment in an older adult patient with ROS1-rearranged lung SCC—the first such report to date.
•
This case suggests that ROS1-targeted therapies may provide clinical benefit in SCC harboring ROS1 rearrangements, emphasizing the need for molecular profiling to guide treatment decisions, regardless of tumor histology.
•
Even at a reduced dose, repotrectinib was effective and well tolerated in this older adult patient, suggesting dose adjustment may be considered based on individual patient characteristics.
•
Comprehensive molecular profiling, including ROS1 testing, should be part of routine diagnostic workup in non-smoking patients with NSCLC, including those with SCC histology, to identify potential actionable targets and optimize treatment strategy.
{"title":"Partial Response to Repotrectinib in ROS1-Rearranged Lung Squamous Cell Carcinoma: A Brief Report","authors":"Yukiko Yoshida , Hajime Asahina , Ken Kuwahara , Hidenori Mizugaki , Noriyuki Yamada , Hiroshi Yokouchi , Naohiro Nomura , Yoshihiro Matsuno , Satoshi Oizumi","doi":"10.1016/j.cllc.2026.01.002","DOIUrl":"10.1016/j.cllc.2026.01.002","url":null,"abstract":"<div><div><ul><li><span>•</span><span><div>ROS1 fusions are rare in lung squamous cell carcinoma (SCC), but they can occur, especially in non-smoking patients, highlighting the importance of comprehensive molecular testing even in SCC histology.</div></span></li><li><span>•</span><span><div>Repotrectinib, a next-generation ROS1 tyrosine kinase inhibitor, demonstrated marked tumor regression and good tolerability as first-line treatment in an older adult patient with ROS1-rearranged lung SCC—the first such report to date.</div></span></li><li><span>•</span><span><div>This case suggests that ROS1-targeted therapies may provide clinical benefit in SCC harboring ROS1 rearrangements, emphasizing the need for molecular profiling to guide treatment decisions, regardless of tumor histology.</div></span></li><li><span>•</span><span><div>Even at a reduced dose, repotrectinib was effective and well tolerated in this older adult patient, suggesting dose adjustment may be considered based on individual patient characteristics.</div></span></li><li><span>•</span><span><div>Comprehensive molecular profiling, including ROS1 testing, should be part of routine diagnostic workup in non-smoking patients with NSCLC, including those with SCC histology, to identify potential actionable targets and optimize treatment strategy.</div></span></li></ul></div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 2","pages":"Pages 80-84"},"PeriodicalIF":3.3,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074257","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}
Pub Date : 2026-01-01DOI: 10.1016/j.cllc.2025.11.016
Ivy Riano , Maria A. Velez , Hugo Pomares-Millan , Juan Blaquier , Supriya Peshin , Jill Feldman , Ana I. Velazquez
Introduction
Brain metastases (BM) occur in approximately 20% of lung cancer patients. Despite recent treatment advances, people with BM are often excluded from clinical trials (CT) limiting our understanding of therapy effectiveness. We evaluated how the 2017 ASCO/FDA/Friends of Cancer Research (FoCR) recommendations on inclusion of patients with BM and leptomeningeal disease (LMD) in CT have been adopted by registered lung cancer trials.
Methods
We retrieved U.S.-based phase I/II/III interventional CT from ClinicalTrials.gov enrolling patients with metastatic lung cancer. We evaluated the eligibility criteria of each CT for the inclusion of patients with: (1) BM, and classified them as excluded, partially included, or included; (2) LMD, and classified them as included or excluded. Fisher’s exact tests and odds ratios (OR) were conducted using logistic regression models.
Results
Among 307 CTs reviewed, 75.6% were phase I/II trials and 7.8% evaluated central nervous system (CNS) outcomes. While most trials partially included patients with treated/stable BM (74.3%, n = 228), only 11.4% (n = 35) included patients with active, untreated BM. Patients with LMD were included in 5.8% (n = 18) trials. A statistically significant difference was noted in the inclusion of patients with BM pre and postrecommendations (32.6% pre vs. 53.1% postrecommendations; P = .046), with CNS outcomes more likely evaluated in trials that included active BM or LMD.
Conclusions
There is an increasing trend of including patients with BM in lung cancer CTs since the publication of the 2017 ASCO/FDA/FoCR guidelines. However, patients with LMD and those with active BM continue to be excluded from most lung cancer CTs.
{"title":"Expanding Lung Cancer Clinical Trial Criteria: A Systematic Review on Inclusion of Patients with Brain Metastases and Leptomeningeal Disease","authors":"Ivy Riano , Maria A. Velez , Hugo Pomares-Millan , Juan Blaquier , Supriya Peshin , Jill Feldman , Ana I. Velazquez","doi":"10.1016/j.cllc.2025.11.016","DOIUrl":"10.1016/j.cllc.2025.11.016","url":null,"abstract":"<div><h3>Introduction</h3><div>Brain metastases (BM) occur in approximately 20% of lung cancer patients. Despite recent treatment advances, people with BM are often excluded from clinical trials (CT) limiting our understanding of therapy effectiveness. We evaluated how the 2017 ASCO/FDA/Friends of Cancer Research (FoCR) recommendations on inclusion of patients with BM and leptomeningeal disease (LMD) in CT have been adopted by registered lung cancer trials.</div></div><div><h3>Methods</h3><div>We retrieved U.S.-based phase I/II/III interventional CT from ClinicalTrials.gov enrolling patients with metastatic lung cancer. We evaluated the eligibility criteria of each CT for the inclusion of patients with: (1) BM, and classified them as excluded, partially included, or included; (2) LMD, and classified them as included or excluded. Fisher’s exact tests and odds ratios (OR) were conducted using logistic regression models.</div></div><div><h3>Results</h3><div>Among 307 CTs reviewed, 75.6% were phase I/II trials and 7.8% evaluated central nervous system (CNS) outcomes. While most trials partially included patients with treated/stable BM (74.3%, n = 228), only 11.4% (n = 35) included patients with active, untreated BM. Patients with LMD were included in 5.8% (n = 18) trials. A statistically significant difference was noted in the inclusion of patients with BM pre and postrecommendations (32.6% pre vs. 53.1% postrecommendations; <em>P</em> = .046), with CNS outcomes more likely evaluated in trials that included active BM or LMD.</div></div><div><h3>Conclusions</h3><div>There is an increasing trend of including patients with BM in lung cancer CTs since the publication of the 2017 ASCO/FDA/FoCR guidelines. However, patients with LMD and those with active BM continue to be excluded from most lung cancer CTs.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 1","pages":"Pages 92-98"},"PeriodicalIF":3.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145862290","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}
In pleural mesothelioma (PM), platinum-based chemotherapy and immune checkpoint inhibitors including nivolumab and ipilimumab have been approved but have not shown sufficient therapeutic efficacy, and the development of new therapies is desired. Pembrolizumab, anti-PD-1 antibody and lenvatinib which has inhibitory effect of angiogenesis are also expected to have a therapeutic effect on PM.
Patients and Methods
Twenty-five patients will be enrolled in PENINSULA trial. In induction treatment, study interventions include oral lenvatinib, 8 mg QD, and pembrolizumab, 200 mg, carboplatin (AUC 5 mg/mL/min) or cisplatin (75 mg/m2), and pemetrexed, 500 mg/m2 all given by intravenous (IV) infusion. In maintenance treatment, participants may receive lenvatinib, 20 mg QD, and pembrolizumab, 200 mg. Lenvatinib and pembrolizumab may be given for up to a total of 35 courses. The primary endpoint is overall response rate. The secondary endpoints are progression-free survival, overall survival time, tumor shrinkage (disease control rate), duration of response, best overall response and safety evaluation.
Conclusion
The purpose of this clinical trial is to evaluate the efficacy and safety of lenvatinib in combination with pembrolizumab and standard chemotherapy as first-line therapy in adult patients with PM.
{"title":"Pembrolizumab Plus Platinum Doublet Chemotherapy With Lenvatinib in Unresectable Pleural Mesothelioma as First-Line Treatment (PENINSULA): A Study Protocol for a Single-Arm, Multi-Institutional, Phase II Clinical Trial","authors":"Tetsuya Takagawa , Kanae Takahashi , Yuji Orimoto , Yukie Morisaki , Shinichiro Suna , Takashi Daimon , Takashi Kijima , Kozo Kuribayashi","doi":"10.1016/j.cllc.2025.12.010","DOIUrl":"10.1016/j.cllc.2025.12.010","url":null,"abstract":"<div><h3>Background</h3><div>In pleural mesothelioma (PM), platinum-based chemotherapy and immune checkpoint inhibitors including nivolumab and ipilimumab have been approved but have not shown sufficient therapeutic efficacy, and the development of new therapies is desired. Pembrolizumab, anti-PD-1 antibody and lenvatinib which has inhibitory effect of angiogenesis are also expected to have a therapeutic effect on PM.</div></div><div><h3>Patients and Methods</h3><div>Twenty-five patients will be enrolled in PENINSULA trial. In induction treatment, study interventions include oral lenvatinib, 8 mg QD, and pembrolizumab, 200 mg, carboplatin (AUC 5 mg/mL/min) or cisplatin (75 mg/m<sup>2</sup>), and pemetrexed, 500 mg/m<sup>2</sup> all given by intravenous (IV) infusion. In maintenance treatment, participants may receive lenvatinib, 20 mg QD, and pembrolizumab, 200 mg. Lenvatinib and pembrolizumab may be given for up to a total of 35 courses. The primary endpoint is overall response rate. The secondary endpoints are progression-free survival, overall survival time, tumor shrinkage (disease control rate), duration of response, best overall response and safety evaluation.</div></div><div><h3>Conclusion</h3><div>The purpose of this clinical trial is to evaluate the efficacy and safety of lenvatinib in combination with pembrolizumab and standard chemotherapy as first-line therapy in adult patients with PM.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 2","pages":"Pages 75-79"},"PeriodicalIF":3.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074256","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":"Computed Tomography-Based Radiomics Features Characterize Low and High-Risk Lung Cancer Among People Living With HIV: An Early Report","authors":"Ranjita Poudel , Kristina E. Bowles , Jessica Y. Islam , Oya Altinok , Christine Vinci , Vani N. Simmons , Anna E. Coghill , Matthew B. Schabath","doi":"10.1016/j.cllc.2025.12.008","DOIUrl":"10.1016/j.cllc.2025.12.008","url":null,"abstract":"<div><div><ul><li><span>•</span><span><div>Distinct radiomic features distinguish between high- and low-risk lung cancer patients.</div></span></li><li><span>•</span><span><div>Distinct radiomic features distinguish between among people living with HIV and patients without HIV.</div></span></li><li><span>•</span><span><div>These results support the contention that the biology of lung tumors among people living with HIV versus their counterparts without HIV.</div></span></li><li><span>•</span><span><div>Radiomics features could stratify patients to prevent overtreatment in low-risk patients and guide more aggressive treatment in high-risk patients.</div></span></li></ul></div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 2","pages":"Pages 69-74"},"PeriodicalIF":3.3,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017543","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}
Pub Date : 2025-12-22DOI: 10.1016/j.cllc.2025.12.006
Fabrizio Citarella , Emanuele C. Mingo , Matteo Fiorenti , Marco Russano , Giuseppe Perrone , Giulia La Cava , Valentina Santo , Alessia Vendittelli , Leonardo Brunetti , Cecilia Saracino , Ludovica Esposito , Andrea Malgeri , Sara Ramella , Bruno Vincenzi , Giuseppe Tonini , Alessio Cortellini
Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) widely used in EGFR mutant non-small cell lung cancer (NSCLC). Despite a favorable safety profile, osimertinib-induced lung injury (OILI) remains a rare but clinically significant adverse event. Guidelines recommend permanent discontinuation after severe cases; the rechallenge feasibility in selected patients remains an area of ongoing debate.
We report a case of a 70-year-old patient with EGFR mutant NSCLC who developed grade 4 OILI requiring hospitalization. After resolution with corticosteroids, treatment was switched to afatinib. The patient later progressed showing a de novo EGFR T790M mutation and MET amplification. Considering the limited treatment options, a carefully monitored osimertinib rechallenge at a reduced dose (40 mg/d) was attempted. The patient tolerated treatment without pneumonitis recurrence and achieved disease control for several months before ultimately progressing.
To contextualize this case, we conducted a scoping review of the available literature on osimertinib administration after lung toxicity. Among 27 studies comprising 1645 patients, 449 (27.3%) developed OILI. One hundred eighty nine (42%) were re-treated, either with (114) or without (75) a temporary interruption. The reported risk of recurrence after rechallenge was low, particularly in cases of mild-to-moderate lung injury. In more severe cases the risk was difficult to determine based on the clinical details available.
This study highlights the heterogeneous approaches to OILI and the potential feasibility of rechallenge in selected patients. Given the expanding osimertinib use for early and advanced stage NSCLC, further research is warranted to refine treatment decisions and optimize patient safety.
{"title":"Osimertinib-Induced Lung Injury and Treatment Rechallenge: Clinical Insights From a Case Report With a Comprehensive Literature Review","authors":"Fabrizio Citarella , Emanuele C. Mingo , Matteo Fiorenti , Marco Russano , Giuseppe Perrone , Giulia La Cava , Valentina Santo , Alessia Vendittelli , Leonardo Brunetti , Cecilia Saracino , Ludovica Esposito , Andrea Malgeri , Sara Ramella , Bruno Vincenzi , Giuseppe Tonini , Alessio Cortellini","doi":"10.1016/j.cllc.2025.12.006","DOIUrl":"10.1016/j.cllc.2025.12.006","url":null,"abstract":"<div><div>Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) widely used in EGFR mutant non-small cell lung cancer (NSCLC). Despite a favorable safety profile, osimertinib-induced lung injury (OILI) remains a rare but clinically significant adverse event. Guidelines recommend permanent discontinuation after severe cases; the rechallenge feasibility in selected patients remains an area of ongoing debate.</div><div>We report a case of a 70-year-old patient with EGFR mutant NSCLC who developed grade 4 OILI requiring hospitalization. After resolution with corticosteroids, treatment was switched to afatinib. The patient later progressed showing a de novo EGFR T790M mutation and MET amplification. Considering the limited treatment options, a carefully monitored osimertinib rechallenge at a reduced dose (40 mg/d) was attempted. The patient tolerated treatment without pneumonitis recurrence and achieved disease control for several months before ultimately progressing.</div><div>To contextualize this case, we conducted a scoping review of the available literature on osimertinib administration after lung toxicity. Among 27 studies comprising 1645 patients, 449 (27.3%) developed OILI. One hundred eighty nine (42%) were re-treated, either with (114) or without (75) a temporary interruption. The reported risk of recurrence after rechallenge was low, particularly in cases of mild-to-moderate lung injury. In more severe cases the risk was difficult to determine based on the clinical details available.</div><div>This study highlights the heterogeneous approaches to OILI and the potential feasibility of rechallenge in selected patients. Given the expanding osimertinib use for early and advanced stage NSCLC, further research is warranted to refine treatment decisions and optimize patient safety.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 2","pages":"Pages 59-68"},"PeriodicalIF":3.3,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975195","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}
Pub Date : 2025-12-20DOI: 10.1016/j.cllc.2025.12.005
Pascale Tomasini , Oscar Juan-Vidal , Raffaele Califano , Chien-Chung Lin , Pauline Hulo , Christophe Dooms , Jian Fang , Ana Blasco , Dariusz Kowalski , Jorge Salinas , Govind Babu , Tho Lye Mun , Alessandra Bearz , Veerle Surmont , Clarissa Baldotto , Richu Sharma , Oscar Arrieta , Katarzyna Stencel , Cynthia Card , Alona Zer , Enriqueta Felip
Objective
The MARIPOSA-2 study demonstrated improved progression-free survival with amivantamab and chemotherapy compared with chemotherapy alone in patients with EGFR-mutated locally advanced or metastatic non-small-cell lung cancer (NSCLC) with disease progression on or after treatment with osimertinib. This publication describes the results of patient-reported outcomes (PROs) measures and time to symptomatic progression (TTSP) for 2 treatment arms.
Methods
PRO instruments included the European Organization for Research and Treatment of Cancer Quality of Life (QoL) Questionnaire Core 30 (EORTC QLQ-C30), Patient-Reported Outcomes Measurement Information System Physical Function Short Form 8c, and the NSCLC Symptom Assessment Questionnaire. Changes from baseline were analyzed using mixed-effects models for repeated measures. Treatment comparisons were based on least-squares means. The hazard ratio for TTSP was estimated using a stratified Cox regression model with P value derived from a stratified log-rank test.
Results
Patients received amivantamab-chemotherapy (n = 131) or chemotherapy alone (n = 263). PRO scores were stable over time with little or no group differences in least-squares mean change from baseline. At 6 months postbaseline, 55.1% of patients in the amivantamab-chemotherapy arm reported improved or stable EORTC QLQ-C30 global health status/QoL scores compared with 29.1% in the chemotherapy arm. TTSP was prolonged for the amivantamab-chemotherapy treatment group versus chemotherapy alone (hazard ratio [HR] [95% CI], 0.73 [0.55-0.96]; nominal P = .0259).
Conclusion
PRO results indicate that the clinical benefits of adding amivantamab to chemotherapy were achieved without compromising health-related QoL. Amivantamab-chemotherapy prolonged TTSP versus chemotherapy alone.
{"title":"Patient-Relevant Outcomes From the Phase III MARIPOSA-2 Trial: Amivantamab-Chemotherapy Versus Chemotherapy in EGFR-Mutant Advanced Non-Small-Cell Lung Cancer Following Disease Progression on Osimertinib","authors":"Pascale Tomasini , Oscar Juan-Vidal , Raffaele Califano , Chien-Chung Lin , Pauline Hulo , Christophe Dooms , Jian Fang , Ana Blasco , Dariusz Kowalski , Jorge Salinas , Govind Babu , Tho Lye Mun , Alessandra Bearz , Veerle Surmont , Clarissa Baldotto , Richu Sharma , Oscar Arrieta , Katarzyna Stencel , Cynthia Card , Alona Zer , Enriqueta Felip","doi":"10.1016/j.cllc.2025.12.005","DOIUrl":"10.1016/j.cllc.2025.12.005","url":null,"abstract":"<div><h3>Objective</h3><div>The MARIPOSA-2 study demonstrated improved progression-free survival with amivantamab and chemotherapy compared with chemotherapy alone in patients with EGFR-mutated locally advanced or metastatic non-small-cell lung cancer (NSCLC) with disease progression on or after treatment with osimertinib. This publication describes the results of patient-reported outcomes (PROs) measures and time to symptomatic progression (TTSP) for 2 treatment arms.</div></div><div><h3>Methods</h3><div>PRO instruments included the European Organization for Research and Treatment of Cancer Quality of Life (QoL) Questionnaire Core 30 (EORTC QLQ-C30), Patient-Reported Outcomes Measurement Information System Physical Function Short Form 8c, and the NSCLC Symptom Assessment Questionnaire. Changes from baseline were analyzed using mixed-effects models for repeated measures. Treatment comparisons were based on least-squares means. The hazard ratio for TTSP was estimated using a stratified Cox regression model with <em>P</em> value derived from a stratified log-rank test.</div></div><div><h3>Results</h3><div>Patients received amivantamab-chemotherapy (n = 131) or chemotherapy alone (n = 263). PRO scores were stable over time with little or no group differences in least-squares mean change from baseline. At 6 months postbaseline, 55.1% of patients in the amivantamab-chemotherapy arm reported improved or stable EORTC QLQ-C30 global health status/QoL scores compared with 29.1% in the chemotherapy arm. TTSP was prolonged for the amivantamab-chemotherapy treatment group versus chemotherapy alone (hazard ratio [HR] [95% CI], 0.73 [0.55-0.96]; nominal <em>P</em> = .0259).</div></div><div><h3>Conclusion</h3><div>PRO results indicate that the clinical benefits of adding amivantamab to chemotherapy were achieved without compromising health-related QoL. Amivantamab-chemotherapy prolonged TTSP versus chemotherapy alone.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 2","pages":"Pages 38-47"},"PeriodicalIF":3.3,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975193","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}
Background: Immune checkpoint inhibitors (ICIs) with platinum-doublet chemotherapy (Chemo-ICIs) are used as the standard treatment for advanced non-small cell lung cancer (NSCLC) with performance status (PS) 0 to 1. However, patients with PS2 are often excluded from clinical trials, leading to an evidence gap that makes it difficult to select the optimal treatment strategy. The efficacy and safety of first-line Chemo-ICIs in PS2 remain unclear.
Patients and methods: This multicenter retrospective cohort study analyzed real-world data of 2425 patients with stage IV NSCLC and PS0 to 2 without driver oncogenes. Propensity score matching was used to compare outcomes between patients receiving Chemo and those receiving Chemo-ICIs. Primary endpoints included progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), and the incidence of grade ≥ 3 adverse events.
Results: Among 424 patients with PS2 (median age 71 years; 73% men), 56 received Chemo-ICIs and 117 received Chemo. After matching, median PFS was significantly longer in the Chemo-ICIs group (5.7 vs. 2.3 months; hazard ratio [HR] 0.58 [0.36-0.93]; P = .025), and ORR was higher (43% vs. 21%; P = .02). OS showed a non-significant trend toward improvement (8.0 vs. 6.0 months; HR 0.75 [0.47-1.19]; P = .219). Rates of grade ≥ 3 adverse events were comparable (50.0% vs. 43.6%; P = .514).
Conclusions: Chemo-ICIs significantly improved PFS and ORR compared to Chemo in patients with NSCLC with PS2 without higher toxicity. These findings highlight the clinical relevance of chemoimmunotherapy in patients with PS2 and may help bridge the evidence gap in existing treatment guidelines.
背景：免疫检查点抑制剂（ICIs）联合铂双药化疗（Chemo-ICIs）被用作治疗性能状态（PS）为0 - 1的晚期非小细胞肺癌（NSCLC）的标准治疗。然而，PS2患者经常被排除在临床试验之外，导致证据空白，难以选择最佳治疗策略。一线Chemo-ICIs治疗PS2的疗效和安全性尚不清楚。患者和方法：这项多中心回顾性队列研究分析了2425例无驱动癌基因的IV期NSCLC和PS0至2期患者的真实数据。倾向评分匹配用于比较接受化疗的患者和接受化疗- icis的患者之间的结果。主要终点包括无进展生存期（PFS）、总生存期（OS）、客观缓解率（ORR）和≥3级不良事件发生率。结果：在424例PS2患者中（中位年龄71岁，73%为男性），56例接受了Chemo- icis， 117例接受了Chemo。匹配后，化疗- icis组的中位PFS明显更长（5.7 vs 2.3个月；风险比[HR] 0.58 [0.36-0.93]; P = 0.025）， ORR更高（43% vs 21%; P = 0.02）。OS无明显改善趋势（8.0 vs. 6.0个月；HR 0.75 [0.47-1.19]; P = 0.219）。≥3级不良事件发生率具有可比性（50.0% vs 43.6%; P = .514）。结论：与化疗相比，化疗icis显著改善了NSCLC伴PS2患者的PFS和ORR，且没有更高的毒性。这些发现强调了化疗免疫治疗在PS2患者中的临床相关性，并可能有助于弥补现有治疗指南中的证据差距。
{"title":"Multicenter Real-World Data on First-Line Chemoimmunotherapy in Patients With Advanced Non-Small Cell Lung Cancer and Performance Status 2: WJOG18424L.","authors":"Shunichi Kataoka, Takehito Shukuya, Hiroshi Ohtsu, Taichi Miyawaki, Daichi Fujimoto, Hidetoshi Hayashi, Yukihiro Toi, Toshihide Yokoyama, Teruhumi Kato, Teppei Yamaguchi, Kaoru Tanaka, Satoru Miura, Motohiro Tamiya, Motoko Tachihara, Kohei Otsubo, Yuki Sato, Satoshi Ikeda, Shinya Sakata, Takeshi Masuda, Shinnosuke Takemoto, Nobuyuki Yamamoto, Isamu Okamoto, Kazuhisa Takahashi","doi":"10.1016/j.cllc.2025.12.002","DOIUrl":"https://doi.org/10.1016/j.cllc.2025.12.002","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) with platinum-doublet chemotherapy (Chemo-ICIs) are used as the standard treatment for advanced non-small cell lung cancer (NSCLC) with performance status (PS) 0 to 1. However, patients with PS2 are often excluded from clinical trials, leading to an evidence gap that makes it difficult to select the optimal treatment strategy. The efficacy and safety of first-line Chemo-ICIs in PS2 remain unclear.</p><p><strong>Patients and methods: </strong>This multicenter retrospective cohort study analyzed real-world data of 2425 patients with stage IV NSCLC and PS0 to 2 without driver oncogenes. Propensity score matching was used to compare outcomes between patients receiving Chemo and those receiving Chemo-ICIs. Primary endpoints included progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), and the incidence of grade ≥ 3 adverse events.</p><p><strong>Results: </strong>Among 424 patients with PS2 (median age 71 years; 73% men), 56 received Chemo-ICIs and 117 received Chemo. After matching, median PFS was significantly longer in the Chemo-ICIs group (5.7 vs. 2.3 months; hazard ratio [HR] 0.58 [0.36-0.93]; P = .025), and ORR was higher (43% vs. 21%; P = .02). OS showed a non-significant trend toward improvement (8.0 vs. 6.0 months; HR 0.75 [0.47-1.19]; P = .219). Rates of grade ≥ 3 adverse events were comparable (50.0% vs. 43.6%; P = .514).</p><p><strong>Conclusions: </strong>Chemo-ICIs significantly improved PFS and ORR compared to Chemo in patients with NSCLC with PS2 without higher toxicity. These findings highlight the clinical relevance of chemoimmunotherapy in patients with PS2 and may help bridge the evidence gap in existing treatment guidelines.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145896420","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}
Pub Date : 2025-12-08DOI: 10.1016/j.cllc.2025.12.003
Gregory M.M. Videtic , Christopher W. Fleming , Chandana A. Reddy , Kevin L. Stephans
Purpose
To characterize outcomes for solid organ transplant patients with medically inoperable early-stage lung cancer (ES-LC) treated with lung stereotactic body radiotherapy (SBRT).
Methods
We surveyed our institutional review board-approved prospective lung SBRT data registry from 2003 to 2023 for any transplant patients. Patterns of failure were assessed, as well as overall survival (OS) and disease-free survival (DFS). Univariate prognostic factors for OS and DFS were identified with Cox proportional hazards regression.
Results
Twenty-eight of 1976 definitively treated patients (1.4%) met study criteria. Median follow up was 12.4 months. Patient characteristics included: male (67.9%), median pack-years smoking of 34; median age 70.0 years; median Karnofsky Performance Status (KPS) 80. Organs transplanted were lung (57.2%), liver (21.4%), heart (21.4%). Tumor characteristics included: median size 2.4 cm; 85.7% with biopsy-proven cancer. Toxicity (any grade/type) was reported in 9 (32.1%) patients. Failure patterns were local 21.4%, lobar 7.1%, nodal 10.7% and distant 32.1%. First site of failure was distant in 50.0% patients. Median DFS and OS were 17.1 and 14.5 months, respectively. Increasing pack-years smoking was the only factor associated with increased disease failure on univariate analysis (UVA) (P = .0016). KPS and tumor size were significantly associated with OS on UVA and on multivariable analysis (P = .0075) and (P = .0181), respectively.
Conclusions
Organ transplant patients with inoperable ES-LC had higher than expected rates of local failure, decreased cancer control and poorer overall survival after SBRT. We hypothesize that transplant-associated immunosuppression promotes metastatic progression and a tumor biology resistant to SBRT.
{"title":"Lung SBRT Outcomes for Inoperable Early-Stage Lung Cancer Are Impaired in Patients With Solid Organ Transplants","authors":"Gregory M.M. Videtic , Christopher W. Fleming , Chandana A. Reddy , Kevin L. Stephans","doi":"10.1016/j.cllc.2025.12.003","DOIUrl":"10.1016/j.cllc.2025.12.003","url":null,"abstract":"<div><h3>Purpose</h3><div>To characterize outcomes for solid organ transplant patients with medically inoperable early-stage lung cancer (ES-LC) treated with lung stereotactic body radiotherapy (SBRT).</div></div><div><h3>Methods</h3><div>We surveyed our institutional review board-approved prospective lung SBRT data registry from 2003 to 2023 for any transplant patients. Patterns of failure were assessed, as well as overall survival (OS) and disease-free survival (DFS). Univariate prognostic factors for OS and DFS were identified with Cox proportional hazards regression.</div></div><div><h3>Results</h3><div>Twenty-eight of 1976 definitively treated patients (1.4%) met study criteria. Median follow up was 12.4 months. Patient characteristics included: male (67.9%), median pack-years smoking of 34; median age 70.0 years; median Karnofsky Performance Status (KPS) 80. Organs transplanted were lung (57.2%), liver (21.4%), heart (21.4%). Tumor characteristics included: median size 2.4 cm; 85.7% with biopsy-proven cancer. Toxicity (any grade/type) was reported in 9 (32.1%) patients. Failure patterns were local 21.4%, lobar 7.1%, nodal 10.7% and distant 32.1%. First site of failure was distant in 50.0% patients. Median DFS and OS were 17.1 and 14.5 months, respectively. Increasing pack-years smoking was the only factor associated with increased disease failure on univariate analysis (UVA) (<em>P</em> = .0016). KPS and tumor size were significantly associated with OS on UVA and on multivariable analysis (<em>P</em> = .0075) and (<em>P</em> = .0181), respectively.</div></div><div><h3>Conclusions</h3><div>Organ transplant patients with inoperable ES-LC had higher than expected rates of local failure, decreased cancer control and poorer overall survival after SBRT. We hypothesize that transplant-associated immunosuppression promotes metastatic progression and a tumor biology resistant to SBRT.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 2","pages":"Pages 6-13"},"PeriodicalIF":3.3,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145915439","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":"Selpercatinib-Associated Nephropathy in RET Fusion-Positive Lung Cancer: A Case Successfully Managed With Dose Adjustment and Nephroprotective Therapy","authors":"Kohei Oe , Koichi Saruwatari , Yoshikazu Miyasato , Yutaka Kakizoe , Kaori Mochida , Tsuguhiro Furukawa , Kei Muramoto , Kimitaka Akaike , Yusuke Tomita , Takuro Sakagami","doi":"10.1016/j.cllc.2025.12.001","DOIUrl":"10.1016/j.cllc.2025.12.001","url":null,"abstract":"<div><div><ul><li><span>•</span><span><div>Nephrotic syndrome developed after selpercatinib in RET fusion-positive lung cancer</div></span></li><li><span>•</span><span><div>Renal biopsy revealed podocyte injury and mesangial IgA/IgM deposition</div></span></li><li><span>•</span><span><div>Proteinuria improved with selpercatinib dose reduction and ARB/SGLT2 use</div></span></li><li><span>•</span><span><div>Selpercatinib was successfully continued after nephroprotective intervention</div></span></li></ul></div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 2","pages":"Pages 1-5"},"PeriodicalIF":3.3,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145915440","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}
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