Pub Date : 2025-06-03DOI: 10.1016/j.jtocrr.2025.100850
Oluwaseun F. Ayoade MD, MSHA , Maureen E. Canavan PhD, MPH , Emily J. Zolfaghari MD, MS , Giorgio Caturegli MD , So Yeon Kim MD , Daniel J. Boffa MD, MBA
{"title":"Erratum to ‘Recent Survival Gains in Stage IV NSCLC by Sociodemographic Strata’ [JTO Clinical and Research Reports Volume 6 Issue 4 (2025) 100798]","authors":"Oluwaseun F. Ayoade MD, MSHA , Maureen E. Canavan PhD, MPH , Emily J. Zolfaghari MD, MS , Giorgio Caturegli MD , So Yeon Kim MD , Daniel J. Boffa MD, MBA","doi":"10.1016/j.jtocrr.2025.100850","DOIUrl":"10.1016/j.jtocrr.2025.100850","url":null,"abstract":"","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 12","pages":"Article 100850"},"PeriodicalIF":3.5,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145468352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-27DOI: 10.1016/j.jtocrr.2025.100854
Justin A. Olivera MD, Sara Sakowitz MD, MPH, Mara B. Antonoff MD, FACS
{"title":"An Uneven Playing Field: Survival Gains in Stage IV NSCLC Across Sociodemographic Strata","authors":"Justin A. Olivera MD, Sara Sakowitz MD, MPH, Mara B. Antonoff MD, FACS","doi":"10.1016/j.jtocrr.2025.100854","DOIUrl":"10.1016/j.jtocrr.2025.100854","url":null,"abstract":"","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 8","pages":"Article 100854"},"PeriodicalIF":3.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144330224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-26DOI: 10.1016/j.jtocrr.2025.100851
Omar Elghawy MD, Adam Barsouk MD, Jonathan H. Sussman BS, Benjamin A. Bleiberg MD, Lauren Reed-Guy MD, Christopher D’Avella MD, Aditi Singh MD, Christine Ciunci MD, MSCE, Kyle Robinson MD, John Kosteva MD, Corey Langer MD, Roger B. Cohen MD, Charu Aggarwal MD, MPH, Melina Marmarelis MD, MSCE, Lova Sun MD, MSCE
Background
Limited data are available on late immune-related adverse events (IRAEs) in patients with metastatic NSCLC receiving immunotherapy (ICI) beyond 2 years.
Methods
A single-institution retrospective analysis including patients who received longer than 2 years of ICI therapy for metastatic NSCLC between 2012 and 2023 was performed. Late IRAEs were defined as those occurring longer than 2 years after initiation of ICI therapy. The association of late IRAE with OS and PFS was assessed using an extended Cox regression with late IRAE modeled as a time-varying covariate.
Results
In a cohort of 76 patients who received longer than 2 years of ICI, the median duration of treatment was 41.9 months, and 44 out of 76 (58%) experienced an early IRAE before 2 years. After 2 years on ICI, 38 out of 76 (50%) of patients experienced a late IRAE, many of whom (39%) had no previous early IRAE. Higher rates of late IRAEs were seen in females (p = 0.032), White patients (p = 0.041), and patients with previous grade 2 or higher IRAE (p = 0.020). Late IRAE occurrence was not associated with median progression-free survival or median overall survival.
Conclusions
In patients receiving extended-duration ICI beyond 2 years, late IRAEs were common and often occurred in patients without previous history of IRAE. These findings support consideration of ICI discontinuation at 2 years.
{"title":"Late Immune-Related Adverse Events After At Least Two Years of Immune Checkpoint Inhibitor Therapy: Incidence and Association With Survival in Patients With Advanced NSCLC","authors":"Omar Elghawy MD, Adam Barsouk MD, Jonathan H. Sussman BS, Benjamin A. Bleiberg MD, Lauren Reed-Guy MD, Christopher D’Avella MD, Aditi Singh MD, Christine Ciunci MD, MSCE, Kyle Robinson MD, John Kosteva MD, Corey Langer MD, Roger B. Cohen MD, Charu Aggarwal MD, MPH, Melina Marmarelis MD, MSCE, Lova Sun MD, MSCE","doi":"10.1016/j.jtocrr.2025.100851","DOIUrl":"10.1016/j.jtocrr.2025.100851","url":null,"abstract":"<div><h3>Background</h3><div>Limited data are available on late immune-related adverse events (IRAEs) in patients with metastatic NSCLC receiving immunotherapy (ICI) beyond 2 years.</div></div><div><h3>Methods</h3><div>A single-institution retrospective analysis including patients who received longer than 2 years of ICI therapy for metastatic NSCLC between 2012 and 2023 was performed. Late IRAEs were defined as those occurring longer than 2 years after initiation of ICI therapy. The association of late IRAE with OS and PFS was assessed using an extended Cox regression with late IRAE modeled as a time-varying covariate.</div></div><div><h3>Results</h3><div>In a cohort of 76 patients who received longer than 2 years of ICI, the median duration of treatment was 41.9 months, and 44 out of 76 (58%) experienced an early IRAE before 2 years. After 2 years on ICI, 38 out of 76 (50%) of patients experienced a late IRAE, many of whom (39%) had no previous early IRAE. Higher rates of late IRAEs were seen in females (<em>p</em> = 0.032), White patients (<em>p</em> = 0.041), and patients with previous grade 2 or higher IRAE (<em>p</em> = 0.020). Late IRAE occurrence was not associated with median progression-free survival or median overall survival.</div></div><div><h3>Conclusions</h3><div>In patients receiving extended-duration ICI beyond 2 years, late IRAEs were common and often occurred in patients without previous history of IRAE. These findings support consideration of ICI discontinuation at 2 years.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 9","pages":"Article 100851"},"PeriodicalIF":3.5,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-26DOI: 10.1016/j.jtocrr.2025.100853
J.W. Tijmen van der Wel MD , Merel Jebbink MD , Vincent van der Noort PhD , Ferry Lalezari MD, PhD , Daan van den Broek PhD , Gerrina Ruiter MD, PhD , Jacobus A. Burgers MD, PhD , Paul Baas MD, PhD , Anne S.R. van Lindert MD , Eva E. van der Wall MD , Lisanne E.A. Kastelijn MD, PhD , Marrit Vermeulen BSc , Linda J.W. Bosch PhD , Kim Monkhorst MD, PhD , Mirjam C. Boelens PhD , Egbert F. Smit MD, PhD , Adrianus J. de Langen MD, PhD
Introduction
In osimertinib-treated EGFR mutation (EGFRm)–positive NSCLC, resistance inevitably occurs. Early resistance mechanism (RM) detection by circulating tumor DNA (ctDNA) in plasma and consecutive targeted treatment may delay progressive disease (PD). In this multicenter prospective study, we evaluated the detection rate and time interval of RM emergence in plasma ctDNA before radiologic PD.
Methods
Patients with EGFRm–positive NSCLC, treated with second- or third-line osimertinib, underwent computed tomography of the thorax and ctDNA analysis (Roche AVENIO expanded panel, research use only [Roche Sequencing Solutions, Roche, Basel, Switzerland]) at baseline and every 8 weeks for response evaluation and EGFRm and RM detection. If MET amplification preceded PD, crizotinib was to be added to osimertinib. Other RMs were monitored but not acted on. After PD, patients underwent a tumor biopsy.
Results
Of the 21 evaluable patients, 18 had detectable ctDNA at baseline. In patients with undetectable ctDNA at baseline, ctDNA remained undetectable during treatment. In the 17 out of 18 (94%) patients with detectable ctDNA, PD occurred. In seven out of 21 patients (33%), the EGFRm variant allele frequency increase preceded radiologic PD with a median interval of 9 weeks (range 7–34). In seven out of 21 patients (33%), at least one RM was detected before PD, and the median interval was 14 weeks (range 7–34). Three had one or more RM in ctDNA at baseline. No MET amplification was observed, and treatment with crizotinib was not initiated in any patient. After PD, 16 biopsies were obtained. Five confirmed the RM detected in plasma, five biopsies revealed additional RMs, and six harbored no RM.
Conclusions
In 33% of patients treated with second- or third-line osimertinib, RMs in plasma preceded PD by a median of 14 weeks, suggesting an opportunity for early treatment adjustment, potentially extending tyrosine kinase inhibitor treatment duration.
{"title":"Longitudinal Circulating Tumor DNA–Guided Resistance Analysis During Second-Line Osimertinib Treatment","authors":"J.W. Tijmen van der Wel MD , Merel Jebbink MD , Vincent van der Noort PhD , Ferry Lalezari MD, PhD , Daan van den Broek PhD , Gerrina Ruiter MD, PhD , Jacobus A. Burgers MD, PhD , Paul Baas MD, PhD , Anne S.R. van Lindert MD , Eva E. van der Wall MD , Lisanne E.A. Kastelijn MD, PhD , Marrit Vermeulen BSc , Linda J.W. Bosch PhD , Kim Monkhorst MD, PhD , Mirjam C. Boelens PhD , Egbert F. Smit MD, PhD , Adrianus J. de Langen MD, PhD","doi":"10.1016/j.jtocrr.2025.100853","DOIUrl":"10.1016/j.jtocrr.2025.100853","url":null,"abstract":"<div><h3>Introduction</h3><div>In osimertinib-treated EGFR mutation (EGFRm)–positive NSCLC, resistance inevitably occurs. Early resistance mechanism (RM) detection by circulating tumor DNA (ctDNA) in plasma and consecutive targeted treatment may delay progressive disease (PD). In this multicenter prospective study, we evaluated the detection rate and time interval of RM emergence in plasma ctDNA before radiologic PD.</div></div><div><h3>Methods</h3><div>Patients with EGFRm–positive NSCLC, treated with second- or third-line osimertinib, underwent computed tomography of the thorax and ctDNA analysis (Roche AVENIO expanded panel, research use only [Roche Sequencing Solutions, Roche, Basel, Switzerland]) at baseline and every 8 weeks for response evaluation and EGFRm and RM detection. If MET amplification preceded PD, crizotinib was to be added to osimertinib. Other RMs were monitored but not acted on. After PD, patients underwent a tumor biopsy.</div></div><div><h3>Results</h3><div>Of the 21 evaluable patients, 18 had detectable ctDNA at baseline. In patients with undetectable ctDNA at baseline, ctDNA remained undetectable during treatment. In the 17 out of 18 (94%) patients with detectable ctDNA, PD occurred. In seven out of 21 patients (33%), the EGFRm variant allele frequency increase preceded radiologic PD with a median interval of 9 weeks (range 7–34). In seven out of 21 patients (33%), at least one RM was detected before PD, and the median interval was 14 weeks (range 7–34). Three had one or more RM in ctDNA at baseline. No MET amplification was observed, and treatment with crizotinib was not initiated in any patient. After PD, 16 biopsies were obtained. Five confirmed the RM detected in plasma, five biopsies revealed additional RMs, and six harbored no RM.</div></div><div><h3>Conclusions</h3><div>In 33% of patients treated with second- or third-line osimertinib, RMs in plasma preceded PD by a median of 14 weeks, suggesting an opportunity for early treatment adjustment, potentially extending tyrosine kinase inhibitor treatment duration.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 9","pages":"Article 100853"},"PeriodicalIF":3.5,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144739621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-26DOI: 10.1016/j.jtocrr.2025.100852
Maira A. Castañeda-Avila PhD, MS , Eduardo J. Santiago-Rodríguez PhD, MPH , William Rodríguez-Cintrón MD, MPH , Coral Olazagasti MD , Efrén J. Flores MD , Estelamari Rodríguez MD, MPH , Ana I. Velázquez Mañana MD, MSc , Yomayra Otero-Domínguez MD, MS , Eduardo R. Núñez MD, MS
Importance
Lung cancer screening (LCS) with yearly low-dose computed tomography reduces lung cancer mortality, but uptake remains low. Puerto Rico, a U.S. territory, faces significant barriers to LCS implementation, but data on LCS eligibility and use are limited.
Objective
This study aimed to estimate the number of individuals eligible for LCS in Puerto Rico and assess the prevalence of LCS use and up-to-date status compared with U.S. Hispanic and non-Hispanic populations.
Design, Setting, and Participants
This cross-sectional study analyzed data from the 2022 Behavioral Risk Factor Surveillance System, a population-based telephone survey. Adults eligible for LCS per 2021 U.S. Preventive Services Task Force guidelines (aged 50–80 years, ≥20 pack-year smoking history, current or recent smokers) from Puerto Rico and the United States were included.
Exposures
Participants were categorized into three groups: Puerto Rico residents, U.S. Hispanic, and U.S. non-Hispanic populations.
Primary Outcomes and Measures
The primary outcomes and measures were self-reported receipt of initial LCS (ever had chest CT for screening) and being up to date with LCS (i.e., chest CT in the past year). Multivariable Poisson models estimated adjusted prevalence ratios for LCS outcomes.
Results
After population weighting, 94,955 individuals were eligible for LCS in Puerto Rico, compared with 12.8 million in the U.S., representing 7.9% and 11.9% of their respective populations. The prevalence of self-reported LCS use was 28.4% in Puerto Rico, 27.6% among U.S. Hispanics, and 31.5% among U.S. non-Hispanics. Being up to date with LCS was lower among Puerto Rico residents (9.8%) than among U.S. Hispanics (17.3%) and non-Hispanics (18.1%). Multivariable models found Puerto Rico residents were less likely to be up to date with LCS than were U.S. non-Hispanics (adjusted prevalence ratios, 0.54; 95% CI 0.29–0.99).
Conclusions and Relevance
Fewer than 10% of eligible individuals in Puerto Rico self-reported being up to date with LCS, indicating they are almost half as likely to self-report as eligible individuals in the United States, highlighting significant gaps in care. Implementing high-quality LCS in Puerto Rico is critical to reducing lung cancer mortality and providing equitable lung cancer care.
肺癌筛查（LCS）每年进行低剂量计算机断层扫描可降低肺癌死亡率，但吸收率仍然很低。波多黎各是美国领土，在实施LCS方面面临重大障碍，但关于LCS资格和使用的数据有限。目的本研究旨在估计波多黎各有资格接受LCS治疗的人数，并与美国西班牙裔和非西班牙裔人群进行比较，评估LCS使用的流行程度和最新状况。设计、环境和参与者本横断面研究分析了2022年行为风险因素监测系统的数据，这是一项基于人群的电话调查。根据2021年美国预防服务工作组指南（年龄50-80岁，吸烟史≥20包年，当前或近期吸烟者），来自波多黎各和美国的符合LCS条件的成年人被纳入研究对象。参与者被分为三组：波多黎各居民、美国西班牙裔和美国非西班牙裔人口。主要结果和测量方法主要结果和测量方法是自我报告的初始LCS（曾经做过胸部CT筛查）和最新的LCS（即过去一年的胸部CT）。多变量泊松模型估计LCS结果的校正患病率。结果在人口加权后，波多黎各有94955人符合LCS资格，而美国有1280万人，分别占其人口的7.9%和11.9%。自我报告的LCS使用率在波多黎各为28.4%，在美国西班牙裔中为27.6%，在美国非西班牙裔中为31.5%。波多黎各居民更新LCS的比例（9.8%）低于美国西班牙裔（17.3%）和非西班牙裔（18.1%）。多变量模型发现，波多黎各居民更新LCS的可能性低于美国非西班牙裔居民(调整患病率比，0.54；95% ci 0.29-0.99)。结论和相关性在波多黎各，只有不到10%的符合条件的个人自我报告最新的LCS，这表明他们自我报告的可能性几乎是美国符合条件个人的一半，突出了护理方面的重大差距。在波多黎各实施高质量的LCS对于降低肺癌死亡率和提供公平的肺癌治疗至关重要。
{"title":"Lung Cancer Screening Eligibility, Uptake, and Adherence in Puerto Rico, 2022","authors":"Maira A. Castañeda-Avila PhD, MS , Eduardo J. Santiago-Rodríguez PhD, MPH , William Rodríguez-Cintrón MD, MPH , Coral Olazagasti MD , Efrén J. Flores MD , Estelamari Rodríguez MD, MPH , Ana I. Velázquez Mañana MD, MSc , Yomayra Otero-Domínguez MD, MS , Eduardo R. Núñez MD, MS","doi":"10.1016/j.jtocrr.2025.100852","DOIUrl":"10.1016/j.jtocrr.2025.100852","url":null,"abstract":"<div><h3>Importance</h3><div>Lung cancer screening (LCS) with yearly low-dose computed tomography reduces lung cancer mortality, but uptake remains low. Puerto Rico, a U.S. territory, faces significant barriers to LCS implementation, but data on LCS eligibility and use are limited.</div></div><div><h3>Objective</h3><div>This study aimed to estimate the number of individuals eligible for LCS in Puerto Rico and assess the prevalence of LCS use and up-to-date status compared with U.S. Hispanic and non-Hispanic populations.</div></div><div><h3>Design, Setting, and Participants</h3><div>This cross-sectional study analyzed data from the 2022 Behavioral Risk Factor Surveillance System, a population-based telephone survey. Adults eligible for LCS per 2021 U.S. Preventive Services Task Force guidelines (aged 50–80 years, ≥20 pack-year smoking history, current or recent smokers) from Puerto Rico and the United States were included.</div></div><div><h3>Exposures</h3><div>Participants were categorized into three groups: Puerto Rico residents, U.S. Hispanic, and U.S. non-Hispanic populations.</div></div><div><h3>Primary Outcomes and Measures</h3><div>The primary outcomes and measures were self-reported receipt of initial LCS (ever had chest CT for screening) and being up to date with LCS (i.e., chest CT in the past year). Multivariable Poisson models estimated adjusted prevalence ratios for LCS outcomes.</div></div><div><h3>Results</h3><div>After population weighting, 94,955 individuals were eligible for LCS in Puerto Rico, compared with 12.8 million in the U.S., representing 7.9% and 11.9% of their respective populations. The prevalence of self-reported LCS use was 28.4% in Puerto Rico, 27.6% among U.S. Hispanics, and 31.5% among U.S. non-Hispanics. Being up to date with LCS was lower among Puerto Rico residents (9.8%) than among U.S. Hispanics (17.3%) and non-Hispanics (18.1%). Multivariable models found Puerto Rico residents were less likely to be up to date with LCS than were U.S. non-Hispanics (adjusted prevalence ratios, 0.54; 95% CI 0.29–0.99).</div></div><div><h3>Conclusions and Relevance</h3><div>Fewer than 10% of eligible individuals in Puerto Rico self-reported being up to date with LCS, indicating they are almost half as likely to self-report as eligible individuals in the United States, highlighting significant gaps in care. Implementing high-quality LCS in Puerto Rico is critical to reducing lung cancer mortality and providing equitable lung cancer care.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 8","pages":"Article 100852"},"PeriodicalIF":3.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144330223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-15DOI: 10.1016/j.jtocrr.2025.100844
Anas Gazzah MD , Charles Ricordel MD, PhD , Antoine Italiano MD, PhD , Byoung Chul Cho MD, PhD , Emiliano Calvo MD, PhD , Dong-Wan Kim MD, PhD , Carole Helissey MD , Jin-Soo Kim MD, PhD , Maria Vieito Villar MD , Francois Ghiringhelli HDR , Victor Moreno MD, PhD , Sophie Cousin MD , Luis Paz-Ares MD, PhD , Nathalie Fagniez Pharm D , Mustapha Chadjaa MD , Anne-Laure Bauchet DECVP, PhD , Christine Soufflet MD , Nina Masson MSc , Fabrice Barlesi MD, PhD
Introduction
Tusamitamab ravtansine is an antibody-drug conjugate targeting cells expressing carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) with a maytansinoid payload, DM4. This phase 1b dose-expansion study (NCT02187848) evaluated its safety, pharmacokinetics, and preliminary antitumor activity in patients with nonsquamous NSCLC (NSq NSCLC).
Methods
Patients aged above or equal to 18 years with advanced or metastatic NSq NSCLC, life expectancy more than or equal to 12 weeks, and high (≥2+ intensity in ≥50% of tumor cells) or moderate (≥2+ intensity in 1%–49% of tumor cells) CEACAM5 expression (assessed by immunohistochemistry) received intravenous tusamitamab ravtansine 100 mg/m2 every 2 weeks.
Results
A total of 64 patients with high and 28 with moderate CEACAM5 expression received a median of 8.0 (1–69) and 4.5 (1–38) treatment cycles, respectively. High expressors had 13 confirmed partial responses and 28 stable diseases (objective response rate, 20.3%; 95% confidence interval [CI]: 12.3%–31.7%, p < 0.0001); median duration of response was 6.7 months, and median time to progression was 3.7 months (95% CI: 2.7–5.1 mo). Moderate expressors had two confirmed partial responses (objective response rate, 7.1%; 95% CI: 2.0%–22.7%, p = 0.4117) and 15 stable diseases.
Treatment-emergent adverse events (AEs) occurred in 78.3% of patients (72/92), 37.0% (34/92) of patients required dose modifications, and 5.4% (5/92) discontinued treatment. The most common treatment-emergent AEs included asthenia (37.0%), keratitis (29.3%), and dyspnea (23.9%). Corneal AEs occurred in 38.0% (35/92), typically grade 1/2, reversible, and manageable by dose modifications.
Conclusions
Tusamitamab ravtansine demonstrated a favorable safety profile, objective responses, and antitumor activity in patients with high CEACAM5-expressing NSq NSCLC.
{"title":"Evaluation of the Safety, Pharmacokinetics, and Antitumor Activity of Tusamitamab Ravtansine in Patients With Nonsquamous NSCLC With High or Moderate Expression of Carcinoembryonic Antigen-Related Cell Adhesion Molecule 5","authors":"Anas Gazzah MD , Charles Ricordel MD, PhD , Antoine Italiano MD, PhD , Byoung Chul Cho MD, PhD , Emiliano Calvo MD, PhD , Dong-Wan Kim MD, PhD , Carole Helissey MD , Jin-Soo Kim MD, PhD , Maria Vieito Villar MD , Francois Ghiringhelli HDR , Victor Moreno MD, PhD , Sophie Cousin MD , Luis Paz-Ares MD, PhD , Nathalie Fagniez Pharm D , Mustapha Chadjaa MD , Anne-Laure Bauchet DECVP, PhD , Christine Soufflet MD , Nina Masson MSc , Fabrice Barlesi MD, PhD","doi":"10.1016/j.jtocrr.2025.100844","DOIUrl":"10.1016/j.jtocrr.2025.100844","url":null,"abstract":"<div><h3>Introduction</h3><div>Tusamitamab ravtansine is an antibody-drug conjugate targeting cells expressing carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) with a maytansinoid payload, DM4. This phase 1b dose-expansion study (NCT02187848) evaluated its safety, pharmacokinetics, and preliminary antitumor activity in patients with nonsquamous NSCLC (NSq NSCLC).</div></div><div><h3>Methods</h3><div>Patients aged above or equal to 18 years with advanced or metastatic NSq NSCLC, life expectancy more than or equal to 12 weeks, and high (≥2+ intensity in ≥50% of tumor cells) or moderate (≥2+ intensity in 1%–49% of tumor cells) CEACAM5 expression (assessed by immunohistochemistry) received intravenous tusamitamab ravtansine 100 mg/m<sup>2</sup> every 2 weeks.</div></div><div><h3>Results</h3><div>A total of 64 patients with high and 28 with moderate CEACAM5 expression received a median of 8.0 (1–69) and 4.5 (1–38) treatment cycles, respectively. High expressors had 13 confirmed partial responses and 28 stable diseases (objective response rate, 20.3%; 95% confidence interval [CI]: 12.3%–31.7%, <em>p</em> < 0.0001); median duration of response was 6.7 months, and median time to progression was 3.7 months (95% CI: 2.7–5.1 mo). Moderate expressors had two confirmed partial responses (objective response rate, 7.1%; 95% CI: 2.0%–22.7%, <em>p</em> = 0.4117) and 15 stable diseases.</div><div>Treatment-emergent adverse events (AEs) occurred in 78.3% of patients (72/92), 37.0% (34/92) of patients required dose modifications, and 5.4% (5/92) discontinued treatment. The most common treatment-emergent AEs included asthenia (37.0%), keratitis (29.3%), and dyspnea (23.9%). Corneal AEs occurred in 38.0% (35/92), typically grade 1/2, reversible, and manageable by dose modifications.</div></div><div><h3>Conclusions</h3><div>Tusamitamab ravtansine demonstrated a favorable safety profile, objective responses, and antitumor activity in patients with high CEACAM5-expressing NSq NSCLC.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 10","pages":"Article 100844"},"PeriodicalIF":3.5,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145096129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-15DOI: 10.1016/j.jtocrr.2025.100848
Chul Kim MD , Vanya Aggarwal MD , Gedske Daugaard MD, DMSc , Tianzhi Tang MD , Jaeil Ahn PhD , Benjamin Besse MD, PhD , Nicolas Girard MD, PhD , Giuseppe Giaccone MD, PhD , Peter Meidahl Petersen MD, PhD
<div><h3>Introduction</h3><div>Thymic epithelial tumors (TETs) are rare and include thymomas (T) and thymic carcinomas (TC). Effective treatment options are needed for patients with progressive disease after platinum-based chemotherapy. Preclinical studies demonstrated antitumor activity of selinexor, an inhibitor of the nuclear receptor exportin-1 (XPO1/CRM1), supporting the clinical development of XPO1-targeted therapy for the treatment of TETs. To further assess the safety and efficacy of selinexor in TETs, we conducted two coordinated parallel phase II clinical trials.</div></div><div><h3>Methods</h3><div>This report includes two nearly identical phase II trials, designed to run in parallel, conducted in the United States (NCT03193437) and Europe (Denmark and France; NCT03466827). Analysis was performed on data pooled from both trials. Both trials were nonrandomized, open-label, two-armed phase II trials (arm A: thymoma, arm B: thymic carcinoma) with the same study design. Patients with histologically confirmed, advanced, inoperable TETs who had progressive disease after treatment with at least one platinum-containing chemotherapy regimen were included. In each 4-week cycle, patients received selinexor 60 mg twice weekly for 3 weeks. To improve tolerability, the starting dose was reduced to 40 mg twice weekly during the study. The primary objective was overall response rate (ORR) assessed by Response Evaluation Criteria in Solid Tumors 1.1, with secondary objectives including progression free survival (PFS), overall survival (OS), and adverse events (AEs) assessed per Common Terminology Criteria for Adverse Event version 4.03.</div></div><div><h3>Results</h3><div>A total of 31 patients were enrolled between the two trials: 16 with T and 15 with TC. The median age was 57 (range: 41–81) years, with 17 men and 14 women. The median number of previous systemic therapies was 2 (range: 1–9). The starting dose was 60 mg twice weekly for 29 patients (93.5%) and 40 mg twice weekly for two patients (6.5%). There was one complete response in the TC group (ORR 6.7%; 95% confidence interval [CI]: 1.2%–29.8%) and two partial responses (ORR 12.5%; 95% CI: 3.5%–36.0%) in the T group. Stable disease as the best response was observed in 11 patients (68.6%) with T and 12 patients (80%) with TC. The median duration of selinexor therapy was 4.5 (range: 0.1–44.3) months. The most common treatment-related adverse events (TRAEs) were nausea (83.8%), vomiting (45.2%), anemia (41.9%), fatigue (38.7%), and asthenia (38.7%). The most common grade 3 or higher TRAEs were anemia (16.1%), thrombocytopenia (12.9%), and asthenia (12.9%). Furthermore, 20 patients (64.5%) required dose reductions due to AEs and 20 patients (64.5%) required dose interruptions. In the T group, the median PFS was 13.6 months (95% CI: 6.3–44.3), and the median OS was not reached. In the TC group, the median PFS was 7.8 months (95% CI: 4.3–15.5) and the median OS was 15.5 months (95% CI: 13.0–29.9).
{"title":"Parallel Phase II Clinical Trials of Selinexor in Patients With Advanced Thymoma and Thymic Carcinoma","authors":"Chul Kim MD , Vanya Aggarwal MD , Gedske Daugaard MD, DMSc , Tianzhi Tang MD , Jaeil Ahn PhD , Benjamin Besse MD, PhD , Nicolas Girard MD, PhD , Giuseppe Giaccone MD, PhD , Peter Meidahl Petersen MD, PhD","doi":"10.1016/j.jtocrr.2025.100848","DOIUrl":"10.1016/j.jtocrr.2025.100848","url":null,"abstract":"<div><h3>Introduction</h3><div>Thymic epithelial tumors (TETs) are rare and include thymomas (T) and thymic carcinomas (TC). Effective treatment options are needed for patients with progressive disease after platinum-based chemotherapy. Preclinical studies demonstrated antitumor activity of selinexor, an inhibitor of the nuclear receptor exportin-1 (XPO1/CRM1), supporting the clinical development of XPO1-targeted therapy for the treatment of TETs. To further assess the safety and efficacy of selinexor in TETs, we conducted two coordinated parallel phase II clinical trials.</div></div><div><h3>Methods</h3><div>This report includes two nearly identical phase II trials, designed to run in parallel, conducted in the United States (NCT03193437) and Europe (Denmark and France; NCT03466827). Analysis was performed on data pooled from both trials. Both trials were nonrandomized, open-label, two-armed phase II trials (arm A: thymoma, arm B: thymic carcinoma) with the same study design. Patients with histologically confirmed, advanced, inoperable TETs who had progressive disease after treatment with at least one platinum-containing chemotherapy regimen were included. In each 4-week cycle, patients received selinexor 60 mg twice weekly for 3 weeks. To improve tolerability, the starting dose was reduced to 40 mg twice weekly during the study. The primary objective was overall response rate (ORR) assessed by Response Evaluation Criteria in Solid Tumors 1.1, with secondary objectives including progression free survival (PFS), overall survival (OS), and adverse events (AEs) assessed per Common Terminology Criteria for Adverse Event version 4.03.</div></div><div><h3>Results</h3><div>A total of 31 patients were enrolled between the two trials: 16 with T and 15 with TC. The median age was 57 (range: 41–81) years, with 17 men and 14 women. The median number of previous systemic therapies was 2 (range: 1–9). The starting dose was 60 mg twice weekly for 29 patients (93.5%) and 40 mg twice weekly for two patients (6.5%). There was one complete response in the TC group (ORR 6.7%; 95% confidence interval [CI]: 1.2%–29.8%) and two partial responses (ORR 12.5%; 95% CI: 3.5%–36.0%) in the T group. Stable disease as the best response was observed in 11 patients (68.6%) with T and 12 patients (80%) with TC. The median duration of selinexor therapy was 4.5 (range: 0.1–44.3) months. The most common treatment-related adverse events (TRAEs) were nausea (83.8%), vomiting (45.2%), anemia (41.9%), fatigue (38.7%), and asthenia (38.7%). The most common grade 3 or higher TRAEs were anemia (16.1%), thrombocytopenia (12.9%), and asthenia (12.9%). Furthermore, 20 patients (64.5%) required dose reductions due to AEs and 20 patients (64.5%) required dose interruptions. In the T group, the median PFS was 13.6 months (95% CI: 6.3–44.3), and the median OS was not reached. In the TC group, the median PFS was 7.8 months (95% CI: 4.3–15.5) and the median OS was 15.5 months (95% CI: 13.0–29.9). ","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 9","pages":"Article 100848"},"PeriodicalIF":3.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144672261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-15DOI: 10.1016/j.jtocrr.2025.100849
Jun-Chieh J. Tsay MD, MS , Antonio Velez MD , Destiny Collazo BS , Isaac Laniado MD , Jamie Bessich MD , Vivek Murthy MD , Andrew DeMaio MD , Samaan Rafeq MD , Benjamin Kwok MD , Fares Darawshy MD , Ray Pillai MD , Kendrew Wong MD , Yonghua Li MD, PhD , Rosemary Schluger RN , Alena Lukovnikova BS , Sofia Roldan BS , Matt Blaisdell BS , Fernanda Paz , Kelsey Krolikowski BS , Katherine Gershner MD , Daniel H. Sterman MD
Introduction
Outcomes for NSCLC remain suboptimal. Recent data suggest that cryoablation can generate antitumor immune effects. In this first-in-human phase I clinical trial, we investigated the safety and feasibility of bronchoscopic cryoimmunotherapy (BCI) delivered during standard-of-care bronchoscopy and explored associated systemic immune responses.
Methods
Subjects with known or suspected advanced-stage NSCLC were recruited. BCI was delivered in dose-escalated freeze-thaw cycles to determine maximum dose tolerance. Feasibility assessment was determined with a pre-set goal of achieving successful BCI in more than or equal to 80% of subjects. Safety was assessed by review of BCI-related complications, including grades 2 to 3 bleeding, pneumothorax requiring intervention, and National Cancer Institute Common Terminology Criteria for Adverse Events grade 3 to 5 adverse events. Pre- and post-BCI blood samples were collected to explore changes in the systemic immune profile.
Results
Subjects with predominantly clinical TNM stage 3 or 4 adenocarcinoma or squamous cell carcinoma were enrolled. We reached the maximum dose of 30 seconds with 100% feasibility and no BCI-related adverse events. In peripheral blood analysis, we observed a significant decrease in derived neutrophil-to-lymphocyte ratio in the high-dose BCI group in comparison to the low-dose BCI cohort. We also observed increases in inflammatory cytokines—GM-CSF, IFN-γ, IL-1β, IL-17A, and IL-2—and effector memory T cells post-BCI.
Conclusion
BCI is safe and feasible. In addition, we provide preliminary evidence that at higher dose levels there is a systemic immune response consistent with a cytotoxic profile. Further immune analyses will determine the potential of BCI as an adjunctive therapy in combination with immune checkpoint inhibition in NSCLC treatment.
{"title":"A Phase I Dose-Escalation Clinical Trial of Bronchoscopic Cryoimmunotherapy in Advanced-Stage NSCLC","authors":"Jun-Chieh J. Tsay MD, MS , Antonio Velez MD , Destiny Collazo BS , Isaac Laniado MD , Jamie Bessich MD , Vivek Murthy MD , Andrew DeMaio MD , Samaan Rafeq MD , Benjamin Kwok MD , Fares Darawshy MD , Ray Pillai MD , Kendrew Wong MD , Yonghua Li MD, PhD , Rosemary Schluger RN , Alena Lukovnikova BS , Sofia Roldan BS , Matt Blaisdell BS , Fernanda Paz , Kelsey Krolikowski BS , Katherine Gershner MD , Daniel H. Sterman MD","doi":"10.1016/j.jtocrr.2025.100849","DOIUrl":"10.1016/j.jtocrr.2025.100849","url":null,"abstract":"<div><h3>Introduction</h3><div>Outcomes for NSCLC remain suboptimal. Recent data suggest that cryoablation can generate antitumor immune effects. In this first-in-human phase I clinical trial, we investigated the safety and feasibility of bronchoscopic cryoimmunotherapy (BCI) delivered during standard-of-care bronchoscopy and explored associated systemic immune responses.</div></div><div><h3>Methods</h3><div>Subjects with known or suspected advanced-stage NSCLC were recruited. BCI was delivered in dose-escalated freeze-thaw cycles to determine maximum dose tolerance. Feasibility assessment was determined with a pre-set goal of achieving successful BCI in more than or equal to 80% of subjects. Safety was assessed by review of BCI-related complications, including grades 2 to 3 bleeding, pneumothorax requiring intervention, and National Cancer Institute Common Terminology Criteria for Adverse Events grade 3 to 5 adverse events. Pre- and post-BCI blood samples were collected to explore changes in the systemic immune profile.</div></div><div><h3>Results</h3><div>Subjects with predominantly clinical TNM stage 3 or 4 adenocarcinoma or squamous cell carcinoma were enrolled. We reached the maximum dose of 30 seconds with 100% feasibility and no BCI-related adverse events. In peripheral blood analysis, we observed a significant decrease in derived neutrophil-to-lymphocyte ratio in the high-dose BCI group in comparison to the low-dose BCI cohort. We also observed increases in inflammatory cytokines—GM-CSF, IFN-γ, IL-1β, IL-17A, and IL-2—and effector memory T cells post-BCI.</div></div><div><h3>Conclusion</h3><div>BCI is safe and feasible. In addition, we provide preliminary evidence that at higher dose levels there is a systemic immune response consistent with a cytotoxic profile. Further immune analyses will determine the potential of BCI as an adjunctive therapy in combination with immune checkpoint inhibition in NSCLC treatment.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 8","pages":"Article 100849"},"PeriodicalIF":3.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144480623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Predictive markers for chemotherapy and immunotherapy response in advanced NSCLC are limited, and no objective tool exists to assess immune function, which is critical for treatment outcomes. This study prospectively evaluated the interferon gamma (IFN-γ) release assay (IGRA) as a potential predictor of treatment response and a tool for assessing immune function.
Methods
We enrolled patients with stage IV NSCLC undergoing first-line chemotherapy, EGFR tyrosine kinase inhibitor (TKI) therapy, or any line of single-agent immunotherapy, alongside stage I controls. Peripheral blood samples were collected pre- and post-treatment for IGRA testing using the QuantiFERON-TB Gold In-Tube (QFT-GIT) kit. Phytohemagglutinin-stimulated IFN-γ (PSIG) responses were measured by both QFT-GIT and in-house enzyme-linked immunosorbent assay, with stage IV patients categorized into high- and low-PSIG response groups based on median pretreatment values.
Results
A total of 117 patients were analyzed (32 surgery, 30 EGFR TKI, 25 chemotherapy, 30 immunotherapy). The median PSIG response was significantly higher in stage I patients than stage IV (1420 pg/mL versus 960 pg/mL; p = 0.032). In stage IV, those with driver mutations had higher pretreatment PSIG responses (1278 pg/mL versus 288 pg/mL; p = 0.004). Kaplan–Meier analysis suggested a trend toward longer progression-free and overall survival in the EGFR TKI and immunotherapy groups with higher PSIG responses, though not statistically significant.
Conclusions
Patients with advanced-stage NSCLC exhibited reduced lymphocyte function, and patients with driver mutations correlated to less exhausted lymphocyte. IGRA demonstrates potential as a clinical tool for assessing immune function in these patients.
晚期非小细胞肺癌化疗和免疫治疗反应的预测标志物有限，没有客观的工具来评估免疫功能，而免疫功能对治疗结果至关重要。本研究前瞻性地评估了干扰素γ (IFN-γ)释放试验（IGRA）作为治疗反应的潜在预测因子和评估免疫功能的工具。方法：我们招募了正在接受一线化疗、EGFR酪氨酸激酶抑制剂（TKI）治疗或任何单药免疫治疗的IV期NSCLC患者，以及I期对照。采用QuantiFERON-TB金管（QFT-GIT）试剂盒采集外周血样本进行IGRA检测。采用QFT-GIT和内部酶联免疫吸附法测量植物血凝素刺激的IFN-γ (PSIG)反应，根据中位预处理值将IV期患者分为高PSIG反应组和低PSIG反应组。结果共分析117例患者，其中手术32例，EGFR TKI 30例，化疗25例，免疫治疗30例。I期患者的PSIG应答中位数显著高于IV期(1420 pg/mL vs 960 pg/mL；P = 0.032)。在IV期，驱动突变患者有更高的预处理PSIG反应(1278 pg/mL vs 288 pg/mL；P = 0.004)。Kaplan-Meier分析显示，EGFR TKI组和免疫治疗组的无进展生存期和总生存期较长，PSIG反应较高，但无统计学意义。结论晚期非小细胞肺癌患者淋巴细胞功能降低，驱动突变患者淋巴细胞耗竭程度较低。IGRA显示了作为评估这些患者免疫功能的临床工具的潜力。
{"title":"A Prospective Exploratory Study of Functional Immunity Assessed by Pretreatment Interferon Gamma Release Assay in Relation to Different Systemic Therapies in Patients With Advanced-Stage NSCLC","authors":"Hsu-Ching Huang MD , Han-Jhih Chang MS , Chi-Lu Chiang MD , Hsin-Yi Huang MS , Yung-Hung Luo MD , Yuh-Min Chen MD , Tsu-Hui Shiao MD , Chao-Hua Chiu MD","doi":"10.1016/j.jtocrr.2025.100845","DOIUrl":"10.1016/j.jtocrr.2025.100845","url":null,"abstract":"<div><h3>Introduction</h3><div>Predictive markers for chemotherapy and immunotherapy response in advanced NSCLC are limited, and no objective tool exists to assess immune function, which is critical for treatment outcomes. This study prospectively evaluated the interferon gamma (IFN-γ) release assay (IGRA) as a potential predictor of treatment response and a tool for assessing immune function.</div></div><div><h3>Methods</h3><div>We enrolled patients with stage IV NSCLC undergoing first-line chemotherapy, EGFR tyrosine kinase inhibitor (TKI) therapy, or any line of single-agent immunotherapy, alongside stage I controls. Peripheral blood samples were collected pre- and post-treatment for IGRA testing using the QuantiFERON-TB Gold In-Tube (QFT-GIT) kit. Phytohemagglutinin-stimulated IFN-γ (PSIG) responses were measured by both QFT-GIT and in-house enzyme-linked immunosorbent assay, with stage IV patients categorized into high- and low-PSIG response groups based on median pretreatment values.</div></div><div><h3>Results</h3><div>A total of 117 patients were analyzed (32 surgery, 30 EGFR TKI, 25 chemotherapy, 30 immunotherapy). The median PSIG response was significantly higher in stage I patients than stage IV (1420 pg/mL versus 960 pg/mL; <em>p</em> = 0.032). In stage IV, those with driver mutations had higher pretreatment PSIG responses (1278 pg/mL versus 288 pg/mL; <em>p =</em> 0.004). Kaplan–Meier analysis suggested a trend toward longer progression-free and overall survival in the EGFR TKI and immunotherapy groups with higher PSIG responses, though not statistically significant.</div></div><div><h3>Conclusions</h3><div>Patients with advanced-stage NSCLC exhibited reduced lymphocyte function, and patients with driver mutations correlated to less exhausted lymphocyte. IGRA demonstrates potential as a clinical tool for assessing immune function in these patients.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 8","pages":"Article 100845"},"PeriodicalIF":3.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144330142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The safety of discontinuing immune checkpoint inhibitors (ICIs) because of a durable response in patients with advanced NSCLC remains uncertain, and post-discontinuation survival outcomes based on the reason for cessation are not well defined.
Methods
A pooled analysis was conducted using data from four prospective cohort studies involving 835 patients with advanced NSCLC who discontinued ICIs. Patients were categorized based on discontinuation reasons: durable response; immune-related adverse events (irAEs) (subcategorized by tumor response at discontinuation); non-irAE adverse events; disease progression; and other causes.
Results
Disease progression was the most common reason for ICI discontinuation (N = 528 [63.2%]), followed by irAEs (N = 187 [22.4%]) and tumor response (N = 23 [2.8%]). Regarding response status at ICI discontinuation due to irAEs, complete/partial response (CR/PR) was the most frequent (N = 85), followed by stable disease/not evaluable (SD/NE, N = 69) and disease progression (N = 33). After a median post-discontinuation follow-up of 15.8 months (interquartile range, 6.9–23.2), patients who discontinued because of a response had excellent outcomes, with no deaths and only three progression-free survival events. While post-discontinuation overall survival was comparable between the irAE-CR/PR and irAE-SD/NE groups, ICI therapy ≥12 months was associated with improved post-ICI discontinuation survival in the irAE-CR/PR group.
Conclusions
Discontinuation of ICIs because of a durable tumor response is rare in real-world settings but represents a feasible strategy for patients with advanced NSCLC. Patients in the irAE-CR/PR group had favorable post-ICI discontinuation survival if they received ICI therapy lasting ≥12 months.
{"title":"Post-discontinuation Survival in Patients With Advanced NSCLC Receiving Immune Checkpoint Inhibitors: A Pooled Analysis of Prospective Cohort Studies","authors":"Yusuke Inoue MD, PhD , Yoshihiro Kitahara MD , Masato Karayama MD, PhD , Kazuhiro Asada MD, PhD , Koji Nishimoto MD, PhD , Shun Matsuura MD, PhD , Dai Hashimoto MD, PhD , Masato Fujii MD, PhD , Takashi Matsui MD, PhD , Nao Inami MD , Mikio Toyoshima MD, PhD , Hiroyuki Matsuda MD, PhD , Masaki Ikeda MD, PhD , Mitsuru Niwa MD, PhD , Yusuke Kaida MD, PhD , Masaki Sato MD, PhD , Yasuhiro Ito MD , Hideki Yasui MD, PhD , Yuzo Suzuki MD, PhD , Hironao Hozumi MD, PhD , Takafumi Suda MD, PhD","doi":"10.1016/j.jtocrr.2025.100847","DOIUrl":"10.1016/j.jtocrr.2025.100847","url":null,"abstract":"<div><h3>Introduction</h3><div>The safety of discontinuing immune checkpoint inhibitors (ICIs) because of a durable response in patients with advanced NSCLC remains uncertain, and post-discontinuation survival outcomes based on the reason for cessation are not well defined.</div></div><div><h3>Methods</h3><div>A pooled analysis was conducted using data from four prospective cohort studies involving 835 patients with advanced NSCLC who discontinued ICIs. Patients were categorized based on discontinuation reasons: durable response; immune-related adverse events (irAEs) (subcategorized by tumor response at discontinuation); non-irAE adverse events; disease progression; and other causes.</div></div><div><h3>Results</h3><div>Disease progression was the most common reason for ICI discontinuation (<em>N</em> = 528 [63.2%]), followed by irAEs (<em>N</em> = 187 [22.4%]) and tumor response (<em>N</em> = 23 [2.8%]). Regarding response status at ICI discontinuation due to irAEs, complete/partial response (CR/PR) was the most frequent (<em>N</em> = 85), followed by stable disease/not evaluable (SD/NE, <em>N</em> = 69) and disease progression (<em>N</em> = 33). After a median post-discontinuation follow-up of 15.8 months (interquartile range, 6.9–23.2), patients who discontinued because of a response had excellent outcomes, with no deaths and only three progression-free survival events. While post-discontinuation overall survival was comparable between the irAE-CR/PR and irAE-SD/NE groups, ICI therapy ≥12 months was associated with improved post-ICI discontinuation survival in the irAE-CR/PR group.</div></div><div><h3>Conclusions</h3><div>Discontinuation of ICIs because of a durable tumor response is rare in real-world settings but represents a feasible strategy for patients with advanced NSCLC. Patients in the irAE-CR/PR group had favorable post-ICI discontinuation survival if they received ICI therapy lasting ≥12 months.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 8","pages":"Article 100847"},"PeriodicalIF":3.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144330153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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