Pub Date : 2025-08-26DOI: 10.1016/j.cllc.2025.08.015
Noah H Richardson , Alexander S Watson , Tejas Patil , David Ross Camidge , Nasser H Hanna , Misty D Shields
•
Lorlatinib, a potent CNS penetrant oral ALK tyrosine kinase inhibitor, is approved in multiple countries for the treatment of advanced/metastatic ALK-positive NSCLC. However, data on dose-escalated strategy in patients with isolated CNS progression and prior lorlatinib exposure is lacking.
•
We report the feasibility of using escalated dose of lorlatinib (125-150 mg daily) in 2 patients with metastatic ALK-positive NSCLC and progressive brain metastasis with previous lorlatinib exposure who obtained disease control with multimodality therapies incorporating dose-escalated lorlatinib.
•
Use of dose-escalated lorlatinib was well tolerated, further investigation of dose-escalated lorlatinib for isolated CNS progression in patients on lorlatinib exposure is suggested.
{"title":"Management of Central Nervous System Progression With Dose-Escalated Lorlatinib in ALK-Positive NSCLC: A Report of 2 Cases and Literature Review","authors":"Noah H Richardson , Alexander S Watson , Tejas Patil , David Ross Camidge , Nasser H Hanna , Misty D Shields","doi":"10.1016/j.cllc.2025.08.015","DOIUrl":"10.1016/j.cllc.2025.08.015","url":null,"abstract":"<div><div><ul><li><span>•</span><span><div>Lorlatinib, a potent CNS penetrant oral ALK tyrosine kinase inhibitor, is approved in multiple countries for the treatment of advanced/metastatic ALK-positive NSCLC. However, data on dose-escalated strategy in patients with isolated CNS progression and prior lorlatinib exposure is lacking.</div></span></li><li><span>•</span><span><div>We report the feasibility of using escalated dose of lorlatinib (125-150 mg daily) in 2 patients with metastatic ALK-positive NSCLC and progressive brain metastasis with previous lorlatinib exposure who obtained disease control with multimodality therapies incorporating dose-escalated lorlatinib.</div></span></li><li><span>•</span><span><div>Use of dose-escalated lorlatinib was well tolerated, further investigation of dose-escalated lorlatinib for isolated CNS progression in patients on lorlatinib exposure is suggested.</div></span></li></ul></div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 8","pages":"Pages 680-684"},"PeriodicalIF":3.3,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074648","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 : 2025-08-26DOI: 10.1016/j.cllc.2025.08.011
Ming Gao , Yuanliu Nie , Ting Wang , Fangfang Jing , Fan Zhang , Haitao Tao , Junxun Ma , Lijie Wang , Yi Hu
Objective
To explore the efficacy and safety of immune checkpoint inhibitor (ICI) without pemetrexed as first-line maintenance therapy in driver-gene negative advanced lung adenocarcinoma.
Methods
A retrospective analysis was conducted on patients with advanced lung adenocarcinoma who were treated with pemetrexed and platinum combined with ICI as first-line therapy at PLA General Hospital from January 2019 to December 2023. Clinical data of the patients were collected and followed up. SPSS, GraphPad Prism and R were used to analyze the clinical characteristics and survival of the patients.
Results
A total of 138 patients were included in this study, with a median follow-up time of 38.4 months. The median progression-free survival (PFS) of ICI maintenance group and pemetrexed plus ICI (P + ICI) maintenance group were 16.1 months (95%CI 13.9-18.2) and 11.5 months (95%CI 10.0-13.0). No statistically difference was observed between the 2 groups (P = .19). The median overall survival (OS) was 51.1 months (95% CI 32.5-69.6) for the ICI group and 43.6 months (30.4-56.8) for the P + ICI group, with no statistically difference (P = .55). The objective response rate (ORR) was 52.2% (95%CI 40.4-64.0) in the ICI group and 65.2% (95%CI 54.0-76.4) in the P + ICI group. Treatment-related adverse events (TRAEs) occurred in 91.3% and 92.8% of patients, respectively, while grade ≥ 3 events occurred in 27.5% and 30.4%. No grade 5 adverse reactions occurred.
Conclusion
The maintenance treatment of ICI without pemetrexed showed good therapeutic efficacy and manageable adverse events, which can be an option as the first-line maintenance therapy for patients with driver-gene negative advanced lung adenocarcinoma.
{"title":"Immune Checkpoint Inhibitor Without Pemetrexed for First-line Maintenance Therapy in Advanced Lung Adenocarcinoma: A Real-World Retrospective Study","authors":"Ming Gao , Yuanliu Nie , Ting Wang , Fangfang Jing , Fan Zhang , Haitao Tao , Junxun Ma , Lijie Wang , Yi Hu","doi":"10.1016/j.cllc.2025.08.011","DOIUrl":"10.1016/j.cllc.2025.08.011","url":null,"abstract":"<div><h3>Objective</h3><div>To explore the efficacy and safety of immune checkpoint inhibitor (ICI) without pemetrexed as first-line maintenance therapy in driver-gene negative advanced lung adenocarcinoma.</div></div><div><h3>Methods</h3><div>A retrospective analysis was conducted on patients with advanced lung adenocarcinoma who were treated with pemetrexed and platinum combined with ICI as first-line therapy at PLA General Hospital from January 2019 to December 2023. Clinical data of the patients were collected and followed up. SPSS, GraphPad Prism and R were used to analyze the clinical characteristics and survival of the patients.</div></div><div><h3>Results</h3><div>A total of 138 patients were included in this study, with a median follow-up time of 38.4 months. The median progression-free survival (PFS) of ICI maintenance group and pemetrexed plus ICI (P + ICI) maintenance group were 16.1 months (95%CI 13.9-18.2) and 11.5 months (95%CI 10.0-13.0). No statistically difference was observed between the 2 groups (<em>P</em> = .19). The median overall survival (OS) was 51.1 months (95% CI 32.5-69.6) for the ICI group and 43.6 months (30.4-56.8) for the P + ICI group, with no statistically difference (<em>P</em> = .55). The objective response rate (ORR) was 52.2% (95%CI 40.4-64.0) in the ICI group and 65.2% (95%CI 54.0-76.4) in the P + ICI group. Treatment-related adverse events (TRAEs) occurred in 91.3% and 92.8% of patients, respectively, while grade ≥ 3 events occurred in 27.5% and 30.4%. No grade 5 adverse reactions occurred.</div></div><div><h3>Conclusion</h3><div>The maintenance treatment of ICI without pemetrexed showed good therapeutic efficacy and manageable adverse events, which can be an option as the first-line maintenance therapy for patients with driver-gene negative advanced lung adenocarcinoma.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 8","pages":"Pages e735-e742"},"PeriodicalIF":3.3,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079925","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 : 2025-08-26DOI: 10.1016/j.cllc.2025.08.012
Daisuke Morinaga , Megumi Furuta , Satoshi Morita , Eisaku Miyauchi , Kunihiko Kobayashi , Makoto Maemondo , Hajime Asahina , The North East Japan Study Group
Background
In treatment-naïve advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations, approximately 10% to 15% correspond to uncommon mutations. For patients with EGFR uncommon mutations, monotherapy with either a second-generation EGFR tyrosine kinase inhibitor (TKI), afatinib, or a third-generation EGFR-TKI, osimertinib, is recommended as the initial therapy. However, needs remain unmet for patients with central nervous system (CNS) metastases and those who do not respond adequately to single-agent TKI therapy for EGFR uncommon mutations. The recently published FLAURA2 trial showed that osimertinib in combination with platinum-pemetrexed significantly prolonged progression-free survival (PFS) and provided high disease control compared with osimertinib monotherapy for common mutations. Therefore, we planned this phase II study to evaluate the efficacy and safety of osimertinib in combination with platinum-pemetrexed in treatment-naïve NSCLC patients with EGFR uncommon mutations.
Patients and Methods
Forty patients will be enrolled in the study. The primary endpoint is the objective response rate, and the secondary endpoints include safety, PFS and overall survival in overall patients, patients with and without CNS lesions at baseline and according to mutation subtype.
Conclusions
In this study, we will explore the efficacy and safety of osimertinib in combination with platinum-pemetrexed in treatment-naïve NSCLC patients with EGFR uncommon mutations. Our findings may provide treatment options for patients with EGFR uncommon mutations, especially those with CNS metastases or those requiring more intensive treatment.
{"title":"A Phase 2 Study of Osimertinib in Combination With Platinum-Pemetrexed in Patients With Uncommon Epidermal Growth Factor Receptor-Mutated Advanced Non-Small Cell Lung Cancer (NEJ067/OPAL2)","authors":"Daisuke Morinaga , Megumi Furuta , Satoshi Morita , Eisaku Miyauchi , Kunihiko Kobayashi , Makoto Maemondo , Hajime Asahina , The North East Japan Study Group","doi":"10.1016/j.cllc.2025.08.012","DOIUrl":"10.1016/j.cllc.2025.08.012","url":null,"abstract":"<div><h3>Background</h3><div>In treatment-naïve advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations, approximately 10% to 15% correspond to uncommon mutations. For patients with EGFR uncommon mutations, monotherapy with either a second-generation EGFR tyrosine kinase inhibitor (TKI), afatinib, or a third-generation EGFR-TKI, osimertinib, is recommended as the initial therapy. However, needs remain unmet for patients with central nervous system (CNS) metastases and those who do not respond adequately to single-agent TKI therapy for EGFR uncommon mutations. The recently published FLAURA2 trial showed that osimertinib in combination with platinum-pemetrexed significantly prolonged progression-free survival (PFS) and provided high disease control compared with osimertinib monotherapy for common mutations. Therefore, we planned this phase II study to evaluate the efficacy and safety of osimertinib in combination with platinum-pemetrexed in treatment-naïve NSCLC patients with EGFR uncommon mutations.</div></div><div><h3>Patients and Methods</h3><div>Forty patients will be enrolled in the study. The primary endpoint is the objective response rate, and the secondary endpoints include safety, PFS and overall survival in overall patients, patients with and without CNS lesions at baseline and according to mutation subtype.</div></div><div><h3>Conclusions</h3><div>In this study, we will explore the efficacy and safety of osimertinib in combination with platinum-pemetrexed in treatment-naïve NSCLC patients with EGFR uncommon mutations. Our findings may provide treatment options for patients with EGFR uncommon mutations, especially those with CNS metastases or those requiring more intensive treatment.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 8","pages":"Pages 611-616"},"PeriodicalIF":3.3,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091334","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 : 2025-08-25DOI: 10.1016/j.cllc.2025.08.016
Jinghan Shi, Kuan Xu, Xufeng Liu, Minjun Shi, Chunyu Ji, Bo Ye
Purpose: Lung adenocarcinoma (LUAD) with anaplastic lymphoma kinase (ALK) rearrangements could be targeted with tyrosine kinase inhibitors (TKIs) to improve patient survival. However, the prognostic impacts of ALK rearrangements in resected early-stage LUAD still require clarification. This study evaluated potential clinical characteristics for ALK positivity in stage IA LUAD and identified post-resection prognostic implications.
Methods: A total of 1212 non-mucinous stage IA LUAD patients who underwent curative resection were included in this retrospective analysis, and divided, based on the Ventana assay, into ALK-positive and negative groups. Uni- and multivariate logistic regression analyses investigated relationships between ALK rearrangements and clinical characteristics, while log-rank tests, Kaplan-Meier curves, and multivariate Cox regression analysis identified recurrence-free (RFS) and overall (OS) survival differences between different groups. Cumulative incidence of recurrence curves for different post-surgical groups was also calculated, and Gray's test assessed their differences. Potential confounder impacts were minimized by 1:2 greedy propensity score matching.
Results: Out of 1212 cases of stage IA LUAD, 82 (6.8%) were ALK-positive. ALK-positivity was most strongly associated with tumor spread through air spaces (STAS) and International Association for the Study of Lung Cancer grade 3. STAS-positivity was also associated with worse RFS and OS. ALK- and STAS-positive patients, compared to ALK-negative, had significantly worse RFS and higher likelihood for distant metastases.
Conclusions: ALK rearrangement-positivity in resected stage IA LUAD correlated with more aggressive histological features. STAS- and ALK-positive patients had worse survival and higher metastatic likelihood, compared to ALK-negative. Therefore, targeting STAS- and ALK-positive LUAD with TKIs may improve post-treatment survival rates and reduce metastatic spread.
{"title":"Anaplastic Lymphoma Kinase Rearrangement and Tumor Spread Through Air Spaces Is Associated with Worse Clinical Outcomes for Resected Stage IA Lung Adenocarcinoma.","authors":"Jinghan Shi, Kuan Xu, Xufeng Liu, Minjun Shi, Chunyu Ji, Bo Ye","doi":"10.1016/j.cllc.2025.08.016","DOIUrl":"https://doi.org/10.1016/j.cllc.2025.08.016","url":null,"abstract":"<p><strong>Purpose: </strong>Lung adenocarcinoma (LUAD) with anaplastic lymphoma kinase (ALK) rearrangements could be targeted with tyrosine kinase inhibitors (TKIs) to improve patient survival. However, the prognostic impacts of ALK rearrangements in resected early-stage LUAD still require clarification. This study evaluated potential clinical characteristics for ALK positivity in stage IA LUAD and identified post-resection prognostic implications.</p><p><strong>Methods: </strong>A total of 1212 non-mucinous stage IA LUAD patients who underwent curative resection were included in this retrospective analysis, and divided, based on the Ventana assay, into ALK-positive and negative groups. Uni- and multivariate logistic regression analyses investigated relationships between ALK rearrangements and clinical characteristics, while log-rank tests, Kaplan-Meier curves, and multivariate Cox regression analysis identified recurrence-free (RFS) and overall (OS) survival differences between different groups. Cumulative incidence of recurrence curves for different post-surgical groups was also calculated, and Gray's test assessed their differences. Potential confounder impacts were minimized by 1:2 greedy propensity score matching.</p><p><strong>Results: </strong>Out of 1212 cases of stage IA LUAD, 82 (6.8%) were ALK-positive. ALK-positivity was most strongly associated with tumor spread through air spaces (STAS) and International Association for the Study of Lung Cancer grade 3. STAS-positivity was also associated with worse RFS and OS. ALK- and STAS-positive patients, compared to ALK-negative, had significantly worse RFS and higher likelihood for distant metastases.</p><p><strong>Conclusions: </strong>ALK rearrangement-positivity in resected stage IA LUAD correlated with more aggressive histological features. STAS- and ALK-positive patients had worse survival and higher metastatic likelihood, compared to ALK-negative. Therefore, targeting STAS- and ALK-positive LUAD with TKIs may improve post-treatment survival rates and reduce metastatic spread.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091403","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 : 2025-08-23DOI: 10.1016/j.cllc.2025.08.010
Jeremy Mudd , Hamna Zafar , Grace Mhango , Christopher G. Slatore , Raja Flores , Scott Swanson , Kenneth Rosenzweig , Jeffrey A. Kern , Juan P. Wisnivesky
•
Disparities persist in surgical management of early-stage lung cancer.
•
Candidacy for sub-lobar resection did not vary by patient race/ethnicity.
•
Nor did race/ethnicity influence provider recommendation for sub-lobar resection.
{"title":"Provider Bias in Decision Making About Treatment of Early-stage Lung Cancer With Stereotactic Body Radiation Therapy or Sub-lobar Resection","authors":"Jeremy Mudd , Hamna Zafar , Grace Mhango , Christopher G. Slatore , Raja Flores , Scott Swanson , Kenneth Rosenzweig , Jeffrey A. Kern , Juan P. Wisnivesky","doi":"10.1016/j.cllc.2025.08.010","DOIUrl":"10.1016/j.cllc.2025.08.010","url":null,"abstract":"<div><div><ul><li><span>•</span><span><div>Disparities persist in surgical management of early-stage lung cancer.</div></span></li><li><span>•</span><span><div>Candidacy for sub-lobar resection did not vary by patient race/ethnicity.</div></span></li><li><span>•</span><span><div>Nor did race/ethnicity influence provider recommendation for sub-lobar resection.</div></span></li></ul></div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 8","pages":"Pages e731-e734.e1"},"PeriodicalIF":3.3,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130277","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}
For metastatic non-small-cell lung cancer (mNSCLC) patients with oncogenic driver progression after tyrosine kinase inhibitors (TKIs), obtaining a new mutational profile is recommended to assess the mechanism of resistance. The feasibility of that recommendation and its clinical impact remain poorly studied.
Methods
mNSCLC patients with EGFR mutation and ALK or ROS translocation progressing on optimal TKI therapy were screened for inclusion in an immunochemotherapy trial not requiring a new molecular profile determination. This analysis evaluated the rebiopsy rate and its clinical impact.
Results
Among 148 patients, 79 (53.4%) analyzable re-biopsies showed 72/132 (54.6%) with EGFR mutations, 7/13 (53.8%) had ALK translocations and no (0/5) ROS translocations. Seventy-nine re-biopsies were tissue (37, 46.8%), liquid (26, 32.9%) or both samples (16, 20.3%). For patients harboring EGFR mutations, the rebiopsy was not contributive for 12/72 (16.7%), the initial mutation was not found for 9/72 (12.5%) and only the unchanged initial profile was detected for 22/72 (30.6%); new information was provided for 29/72 (40.3%). Among patients with ALK-translocated mNSCLCs, re-biopsies enabled identification of resistance mechanisms for 20%. Overall survival did not differ between patients with rebiopsy and those without.
Conclusions
In this population of patients with oncogenic driver progression under optimal targeted TKIs and in sufficiently good general condition to be included in an immunochemotherapy trial, only half were re-biopsied. Rebiopsy does not seem to improve the outcomes of these patients.
{"title":"Rebiopsy Feasibility and Clinical Impact on Metastatic Non-Small-Cell Lung Cancer With EGFR/ALK/ROS Oncogenic Driver Progression After Optimal Targeted Therapy: A Multicenter Real-World Analysis","authors":"Antoine Bronstein , Hubert Curcio , Isabelle Monnet , Charles Ricordel , Laurence Bigay-Game , Margaux Geier , Chantal Decroisette , Catherine Daniel , Florian Guisier , Aurélie Swalduz , Anne Claire Toffart , Hélène Doubre , Jean Michel Peloni , Dominique Arpin , Hugues Morel , Remi Veillon , Benedicte Clarisse , Christos Chouaïd , Laurent Greillier , Olivier Bylicki","doi":"10.1016/j.cllc.2025.08.009","DOIUrl":"10.1016/j.cllc.2025.08.009","url":null,"abstract":"<div><h3>Background</h3><div>For metastatic non-small-cell lung cancer (mNSCLC) patients with oncogenic driver progression after tyrosine kinase inhibitors (TKIs), obtaining a new mutational profile is recommended to assess the mechanism of resistance. The feasibility of that recommendation and its clinical impact remain poorly studied.</div></div><div><h3>Methods</h3><div>mNSCLC patients with <em>EGFR</em> mutation and <em>ALK</em> or <em>ROS</em> translocation progressing on optimal TKI therapy were screened for inclusion in an immunochemotherapy trial not requiring a new molecular profile determination. This analysis evaluated the rebiopsy rate and its clinical impact.</div></div><div><h3>Results</h3><div>Among 148 patients, 79 (53.4%) analyzable re-biopsies showed 72/132 (54.6%) with <em>EGFR</em> mutations, 7/13 (53.8%) had <em>ALK</em> translocations and no (0/5) <em>ROS</em> translocations. Seventy-nine re-biopsies were tissue (37, 46.8%), liquid (26, 32.9%) or both samples (16, 20.3%). For patients harboring <em>EGFR</em> mutations, the rebiopsy was not contributive for 12/72 (16.7%), the initial mutation was not found for 9/72 (12.5%) and only the unchanged initial profile was detected for 22/72 (30.6%); new information was provided for 29/72 (40.3%). Among patients with <em>ALK</em>-translocated mNSCLCs, re-biopsies enabled identification of resistance mechanisms for 20%. Overall survival did not differ between patients with rebiopsy and those without.</div></div><div><h3>Conclusions</h3><div>In this population of patients with oncogenic driver progression under optimal targeted TKIs and in sufficiently good general condition to be included in an immunochemotherapy trial, only half were re-biopsied. Rebiopsy does not seem to improve the outcomes of these patients.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 8","pages":"Pages e724-e730"},"PeriodicalIF":3.3,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063279","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}
Recent advances in cancer management may have transformed the overall prognosis of patients undergoing lung cancer resection. This study aimed to assess the changes in the long-term survival of patients undergoing surgery for lung cancer over the last 2 decades and to identify the risk factors modulating the postoperative prognosis.
Methods
This single-center retrospective study included nonsmall cell lung cancer patients who underwent lung resection between 2008 and 2020. Exclusion criteria included prior lung cancer or resection, diagnosis of lung metastases, small cell lung cancers, carcinoid tumors, or benign tumors. Multivariate models analyzed determinants of short- and long-term outcomes over time.
Results
Among 2898 lung resections performed, 768 deaths (26.5%) occurred, including 25 (0.9%) in the 30-day postoperative period. Postoperative complications were observed in 1063 cases (36.7%), with 535 (18.5%) being respiratory-related. No significant improvement was observed in 30-day postoperative complications or deaths over time. Conversely, the adjusted hazard ratio (HR) for mortality was 0.72 (95% CI, 0.57-0.92) and 0.59 (95% CI, 0.45-0.78) for the in 2012-2015 and 2016-2020 periods compared to 2008-2011. In multivariate analyses, increasing age, current smoking at the time of surgery, pneumonectomy, advanced cancer stage and lower socioeconomic status were associated with worse outcomes.
Conclusions
Over the past 2 decades, long-term survival after lung cancer resection has significantly improved, despite stable rates of early postoperative complications. Efforts to develop curative treatments for advanced stages remain crucial while public health initiatives must address socioeconomic disparities to further improve lung cancer outcomes.
{"title":"The Changing Landscape of Lung Cancer Resection Outcomes Over the Past two Decades","authors":"Charles-Antoine Guay , Alexandre Suhani , Laurie Perreault , Vicky Mai , Anne-Sophie Laliberté , Catherine Labbé , Steeve Provencher","doi":"10.1016/j.cllc.2025.08.006","DOIUrl":"10.1016/j.cllc.2025.08.006","url":null,"abstract":"<div><h3>Introduction</h3><div>Recent advances in cancer management may have transformed the overall prognosis of patients undergoing lung cancer resection. This study aimed to assess the changes in the long-term survival of patients undergoing surgery for lung cancer over the last 2 decades and to identify the risk factors modulating the postoperative prognosis.</div></div><div><h3>Methods</h3><div>This single-center retrospective study included nonsmall cell lung cancer patients who underwent lung resection between 2008 and 2020. Exclusion criteria included prior lung cancer or resection, diagnosis of lung metastases, small cell lung cancers, carcinoid tumors, or benign tumors. Multivariate models analyzed determinants of short- and long-term outcomes over time.</div></div><div><h3>Results</h3><div>Among 2898 lung resections performed, 768 deaths (26.5%) occurred, including 25 (0.9%) in the 30-day postoperative period. Postoperative complications were observed in 1063 cases (36.7%), with 535 (18.5%) being respiratory-related. No significant improvement was observed in 30-day postoperative complications or deaths over time. Conversely, the adjusted hazard ratio (HR) for mortality was 0.72 (95% CI, 0.57-0.92) and 0.59 (95% CI, 0.45-0.78) for the in 2012-2015 and 2016-2020 periods compared to 2008-2011. In multivariate analyses, increasing age, current smoking at the time of surgery, pneumonectomy, advanced cancer stage and lower socioeconomic status were associated with worse outcomes.</div></div><div><h3>Conclusions</h3><div>Over the past 2 decades, long-term survival after lung cancer resection has significantly improved, despite stable rates of early postoperative complications. Efforts to develop curative treatments for advanced stages remain crucial while public health initiatives must address socioeconomic disparities to further improve lung cancer outcomes.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 8","pages":"Pages e693-e707.e13"},"PeriodicalIF":3.3,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029036","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 : 2025-08-09DOI: 10.1016/j.cllc.2025.08.004
Weibo Cao , Hongtao Duan , Changjian Shao, Xiaolong Yan, Honggang Liu
Background
Neoadjuvant chemotherapy plus anti-programmed death (ligand)-1 (anti-PD-(L)1) inhibitors (chemoimmunotherapy) for early-stage nonsmall cell lung cancer (NSCLC) is under investigation, but differences in pathological response rates between patients who achieved objective responses after 2 versus 3-6 cycles remain unclear.
Methods
We retrospectively enrolled 481 stage II-III NSCLC patients who had 2-6 cycles of neoadjuvant chemoimmunotherapy followed by surgery (June 2018-February 2024). The primary outcomes compared the pathological response (pathological complete response [pCR] and major pathological response [MPR]) between the 2-cycle (n = 99) and 3-6-cycle (n = 382) groups in patients who achieved objective response as well as between objective response rate (ORR) and non-ORR groups.
Results
For patients achieving objective response, pCR (52.7% vs. 47%; odds ratio [OR]: 1.26; 95% confidence interval [CI]: 0.70-2.25; P = .439) and MPR (78.2% vs. 69.9%; OR: 1.54; 95% CI, 0.77-3.08; P = .220) rates in the 2-cycle group were not inferior to the 3-6 cycle group. The ORR group had higher pCR (52.7% vs. 31.8%; OR: 2.39; 95% CI, 1.05-5.46; P = .039) and MPR (78.2% vs. 56.8%; OR: 2.72; 95% CI, 1.14-6.53; P = .025) rates than the non-ORR group for patients undergoing 2 cycles of neoadjuvant therapy. Similar trends for pCR (47.0% vs. 32.8%; OR: 1.82; 95% CI, 1.15-2.87; P = .01) and MPR (69.9% vs. 49.1%; OR: 2.41; 95% CI, 1.54-3.77; P < .001) also occurred in patients undergoing 3-6 cycles of neoadjuvant therapy.
Conclusions
Achieving an objective response following 2 cycles of neoadjuvant chemoimmunotherapy may predict optimal pathological responses in stage II-III NSCLC.
背景：新辅助化疗加抗程序性死亡（配体）-1（抗pd -(L)1）抑制剂（化学免疫疗法）治疗早期非小细胞肺癌（NSCLC）正在研究中，但在2个周期和3-6个周期后达到客观反应的患者之间的病理反应率差异尚不清楚。方法：我们回顾性纳入481例II-III期NSCLC患者，这些患者在2018年6月至2024年2月期间接受了2-6个周期的新辅助化学免疫治疗并进行了手术。主要结局比较2周期（n = 99）和3-6周期（n = 382）患者客观缓解的病理反应（病理完全缓解[pCR]和主要病理反应[MPR]）以及客观缓解率（ORR）和非ORR组之间的差异。结果：对于获得客观缓解的患者，2周期组的pCR （52.7% vs 47%；优势比[OR]: 1.26； 95%可信区间[CI]: 0.70-2.25; P = .439）和MPR （78.2% vs. 69.9%; OR: 1.54; 95% CI, 0.77-3.08; P = .220）率不低于3-6周期组。接受2个周期新辅助治疗的患者，ORR组的pCR （52.7% vs. 31.8%; OR: 2.39; 95% CI, 1.05-5.46; P = 0.039）和MPR （78.2% vs. 56.8%; OR: 2.72; 95% CI, 1.14-6.53; P = 0.025）率高于非ORR组。在接受3-6个周期新辅助治疗的患者中，pCR（47.0%对32.8%;OR: 1.82; 95% CI, 1.15-2.87; P = 0.01）和MPR（69.9%对49.1%;OR: 2.41; 95% CI, 1.54-3.77; P < 0.001）也出现了类似的趋势。结论：在2个周期的新辅助化疗免疫治疗后达到客观反应可能预测II-III期NSCLC的最佳病理反应。
{"title":"Achieving an Objective Response Following Two Cycles of Neoadjuvant Chemotherapy Plus Anti-PD-(L)1 Inhibitors Might Predict the Optimal Pathological Response in Resectable Stage II-III Nonsmall Cell Lung Cancer","authors":"Weibo Cao , Hongtao Duan , Changjian Shao, Xiaolong Yan, Honggang Liu","doi":"10.1016/j.cllc.2025.08.004","DOIUrl":"10.1016/j.cllc.2025.08.004","url":null,"abstract":"<div><h3>Background</h3><div>Neoadjuvant chemotherapy plus anti-programmed death (ligand)-1 (anti-PD-(L)1) inhibitors (chemoimmunotherapy) for early-stage nonsmall cell lung cancer (NSCLC) is under investigation, but differences in pathological response rates between patients who achieved objective responses after 2 versus 3-6 cycles remain unclear.</div></div><div><h3>Methods</h3><div>We retrospectively enrolled 481 stage II-III NSCLC patients who had 2-6 cycles of neoadjuvant chemoimmunotherapy followed by surgery (June 2018-February 2024). The primary outcomes compared the pathological response (pathological complete response [pCR] and major pathological response [MPR]) between the 2-cycle (<em>n</em> = 99) and 3-6-cycle (<em>n</em> = 382) groups in patients who achieved objective response as well as between objective response rate (ORR) and non-ORR groups.</div></div><div><h3>Results</h3><div>For patients achieving objective response, pCR (52.7% vs. 47%; odds ratio [OR]: 1.26; 95% confidence interval [CI]: 0.70-2.25; <em>P</em> = .439) and MPR (78.2% vs. 69.9%; OR: 1.54; 95% CI, 0.77-3.08; <em>P</em> = .220) rates in the 2-cycle group were not inferior to the 3-6 cycle group. The ORR group had higher pCR (52.7% vs. 31.8%; OR: 2.39; 95% CI, 1.05-5.46; <em>P</em> = .039) and MPR (78.2% vs. 56.8%; OR: 2.72; 95% CI, 1.14-6.53; <em>P</em> = .025) rates than the non-ORR group for patients undergoing 2 cycles of neoadjuvant therapy. Similar trends for pCR (47.0% vs. 32.8%; OR: 1.82; 95% CI, 1.15-2.87; <em>P</em> = .01) and MPR (69.9% vs. 49.1%; OR: 2.41; 95% CI, 1.54-3.77; <em>P</em> < .001) also occurred in patients undergoing 3-6 cycles of neoadjuvant therapy.</div></div><div><h3>Conclusions</h3><div>Achieving an objective response following 2 cycles of neoadjuvant chemoimmunotherapy may predict optimal pathological responses in stage II-III NSCLC.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 7","pages":"Pages 573-582"},"PeriodicalIF":3.3,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999790","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}
Repotrectinib is a next-generation ROS1 tyrosine kinase inhibitor that demonstrates clinical activity against the ROS1 G2032R resistance mutation, commonly acquired after treatment with crizotinib and entrectinib. Preclinical studies have shown that repotrectinib has potent activity against another solvent-front resistance mutation, D2033N, although clinical data regarding its efficacy in this setting remain lacking.
•
We present the first case of a patient with advanced ROS1-positive non-small cell lung cancer (NSCLC) harboring the D2033N mutation detected by comprehensive genomic profiling, who experienced clinical benefit from repotrectinib after 11 prior lines of systemic therapy.
•
Repotrectinib resulted in a marked clinical and radiographic response. Although the patient developed neurally mediated syncope after initiation, the adverse event was managed by temporary treatment interruption, dose reduction, and co-administration of adrenergic α1 receptor agonist.
•
This report highlights the potential clinical activity of repotrectinib against the ROS1 D2033N mutation in heavily pretreated patients. Our findings underscore the utility of comprehensive genomic profiling in identifying resistance mutations and support the feasibility of late-line repotrectinib treatment with appropriate supportive care and dose modification strategies.
{"title":"First Clinical Evidence of Repotrectinib Efficacy in ROS1-Rearranged NSCLC With a D2033N Resistance Mutation: Case Report","authors":"Yukiko Yoshida , Hiroshi Yokouchi , Hidenori Mizugaki , Noriyuki Yamada , Hajime Asahina , Hitoki Inoue , Masaharu Nishimura , Satoshi Oizumi","doi":"10.1016/j.cllc.2025.08.005","DOIUrl":"10.1016/j.cllc.2025.08.005","url":null,"abstract":"<div><div><ul><li><span>•</span><span><div>Repotrectinib is a next-generation ROS1 tyrosine kinase inhibitor that demonstrates clinical activity against the <em>ROS1</em> G2032R resistance mutation, commonly acquired after treatment with crizotinib and entrectinib. Preclinical studies have shown that repotrectinib has potent activity against another solvent-front resistance mutation, D2033N, although clinical data regarding its efficacy in this setting remain lacking.</div></span></li><li><span>•</span><span><div>We present the first case of a patient with advanced <em>ROS1</em>-positive non-small cell lung cancer (NSCLC) harboring the D2033N mutation detected by comprehensive genomic profiling, who experienced clinical benefit from repotrectinib after 11 prior lines of systemic therapy.</div></span></li><li><span>•</span><span><div>Repotrectinib resulted in a marked clinical and radiographic response. Although the patient developed neurally mediated syncope after initiation, the adverse event was managed by temporary treatment interruption, dose reduction, and co-administration of adrenergic α1 receptor agonist.</div></span></li><li><span>•</span><span><div>This report highlights the potential clinical activity of repotrectinib against the <em>ROS1</em> D2033N mutation in heavily pretreated patients. Our findings underscore the utility of comprehensive genomic profiling in identifying resistance mutations and support the feasibility of late-line repotrectinib treatment with appropriate supportive care and dose modification strategies.</div></span></li></ul></div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 8","pages":"Pages e688-e692"},"PeriodicalIF":3.3,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991637","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 : 2025-08-06DOI: 10.1016/j.cllc.2025.08.003
Rosalyn Marar , Claire Bai , Eric Hansen , Christina M. Zettler , Andrew J. Belli , Laura L. Fernandes , Ching-Kun Wang , Kaushal Parikh
Purpose
This study analyzed the comparative effectiveness of immune-checkpoint inhibitor (ICI) monotherapy versus ICI+chemotherapy (CIT) in the first-line (1L) setting among metastatic NSCLC (mNSCLC) patients with ≥ 50% programmed death-ligand 1 (PD-L1) expression, and without epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and c-ros oncogene 1 (ROS1) alterations.
Methods
Patients were identified from COTA’s real-world (rw) database meeting the criteria: aged ≥ 18 years at diagnosis with mNSCLC on or after January 1, 2017, ≥ 50% PD-L1 expression, negative for EGFR, ALK, and ROS1 mutations, and received 1L ICI monotherapy or CIT. Characteristics and treatment patterns were summarized overall and by treatment group. Rw time to next treatment (rwTTNT), progression-free survival (rwPFS), and overall survival (rwOS) were summarized using Kaplan-Meier methodology. The inverse probability of treatment weighting method was used to balance baseline characteristics for adjusted analyses.
Results
Of 311 patients, 178 received ICI monotherapy and 133 received CIT. Adjusted median rwTTNT was 11.31 months for the CIT group compared to 7.63 for the ICI group (HR: 0.68, 95% CI: 0.50, 0.93). Adjusted rwPFS for the CIT group vs. ICI group was 8.78 and 5.56 months, respectively (HR: 0.82, 95% CI: 0.61, 1.11), and adjusted median rwOS for CIT and ICI was 23.08 and 20.28 months, respectively (HR: 0.83, 95% CI: 0.59, 1.18).
Conclusions
Although adjusted rwTTNT differed by treatment group, this did not translate to a significant difference in survival. Among mNSCLC patients with high PD-L1 expression, the addition of chemotherapy to ICI did not improve survival.
{"title":"Treatment Patterns and Outcomes of Non-Small Cell Lung Cancer with High PD-L1 Expression using Real World Evidence","authors":"Rosalyn Marar , Claire Bai , Eric Hansen , Christina M. Zettler , Andrew J. Belli , Laura L. Fernandes , Ching-Kun Wang , Kaushal Parikh","doi":"10.1016/j.cllc.2025.08.003","DOIUrl":"10.1016/j.cllc.2025.08.003","url":null,"abstract":"<div><h3>Purpose</h3><div>This study analyzed the comparative effectiveness of immune-checkpoint inhibitor (ICI) monotherapy versus ICI+chemotherapy (CIT) in the first-line (1L) setting among metastatic NSCLC (mNSCLC) patients with ≥ 50% programmed death-ligand 1 (PD-L1) expression, and without epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and c-ros oncogene 1 (ROS1) alterations.</div></div><div><h3>Methods</h3><div>Patients were identified from COTA’s real-world (rw) database meeting the criteria: aged ≥ 18 years at diagnosis with mNSCLC on or after January 1, 2017, ≥ 50% PD-L1 expression, negative for EGFR, ALK, and ROS1 mutations, and received 1L ICI monotherapy or CIT. Characteristics and treatment patterns were summarized overall and by treatment group. Rw time to next treatment (rwTTNT), progression-free survival (rwPFS), and overall survival (rwOS) were summarized using Kaplan-Meier methodology. The inverse probability of treatment weighting method was used to balance baseline characteristics for adjusted analyses.</div></div><div><h3>Results</h3><div>Of 311 patients, 178 received ICI monotherapy and 133 received CIT. Adjusted median rwTTNT was 11.31 months for the CIT group compared to 7.63 for the ICI group (HR: 0.68, 95% CI: 0.50, 0.93). Adjusted rwPFS for the CIT group vs. ICI group was 8.78 and 5.56 months, respectively (HR: 0.82, 95% CI: 0.61, 1.11), and adjusted median rwOS for CIT and ICI was 23.08 and 20.28 months, respectively (HR: 0.83, 95% CI: 0.59, 1.18).</div></div><div><h3>Conclusions</h3><div>Although adjusted rwTTNT differed by treatment group, this did not translate to a significant difference in survival. Among mNSCLC patients with high PD-L1 expression, the addition of chemotherapy to ICI did not improve survival.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 7","pages":"Pages 564-572.e4"},"PeriodicalIF":3.3,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945593","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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