Evidence of immune checkpoint inhibitors (ICIs) combined with chemotherapy for older patients with NSCLC is limited. This real-world study compared the efficacy and safety of atezolizumab plus chemotherapy (ACT) with those of pembrolizumab plus chemotherapy (PCT) for older patients with advanced nonsquamous NSCLC.
Methods
This multicenter, retrospective study included 288 patients 65 years or older with advanced or recurrent nonsquamous NSCLC who received PCT or ACT as first-line treatment at 13 institutions in Japan. After one-to-one propensity score matching, overall survival (OS), the incidence of grade 3 or higher treatment-related adverse events, and all-grade pneumonitis of the PCT and ACT groups were compared.
Results
After propensity score matching, 54 patients were included in each of the groups. OS did not significantly differ between the PCT and ACT groups. The median OS was 16.6 months for both groups. Compared with the PCT group, the ACT group had a hazard ratio of 1.09 (95% confidence interval [CI]: 0.68–1.74; p = 0.7). Grade 3 or higher adverse events occurred in 40.7% and 33.3% of patients in the PCT and ACT groups, respectively (p = 0.55). The incidence of treatment-related pneumonitis of the PCT group was significantly higher (29.6%, including 11 grade ≥3 cases) than that of the ACT group (5.6%, including two grade ≥3 cases) (p = 0.002).
Conclusions
ACT may be associated with a more favorable safety profile than that of PCT for the Japanese population; therefore, ACT could be considered a treatment option for older patients with advanced nonsquamous NSCLC.
免疫检查点抑制剂（ICIs）联合化疗治疗老年非小细胞肺癌的证据有限。这项现实世界的研究比较了atezolizumab加化疗（ACT）和派姆单抗加化疗（PCT）对老年晚期非鳞状NSCLC患者的疗效和安全性。方法本多中心回顾性研究纳入了288例65岁及以上晚期或复发性非鳞状NSCLC患者，这些患者在日本13家机构接受了PCT或ACT作为一线治疗。一对一倾向评分匹配后，比较PCT组和ACT组的总生存率（OS）、3级及以上治疗相关不良事件发生率和全级别肺炎。结果经倾向评分匹配后，两组共纳入54例患者。PCT组和ACT组间OS无显著差异。两组的中位OS均为16.6个月。与PCT组相比，ACT组的风险比为1.09（95%可信区间[CI]: 0.68-1.74; p = 0.7）。PCT组和ACT组3级及以上不良事件发生率分别为40.7%和33.3% （p = 0.55）。PCT组治疗相关性肺炎的发生率（29.6%，包括11例≥3级）显著高于ACT组（5.6%，包括2例≥3级）（p = 0.002）。结论：在日本人群中，sact可能比PCT具有更有利的安全性；因此，ACT可以被认为是老年晚期非鳞状NSCLC患者的一种治疗选择。
{"title":"A Multicenter, Retrospective, Real-World Study of Atezolizumab Plus Chemotherapy and Pembrolizumab Plus Chemotherapy for Older Patients With NSCLC","authors":"Kensuke Kanaoka MD , Kinnosuke Matsumoto MD , Takayuki Shiroyama MD, PhD , Akihiro Tsukaguchi MD , Nao Shoshihara MD , Koki Moritomo MD , Yuhei Kinehara MD, PhD , Yasuhiro Mihashi MD , Tomoki Kuge MD , Midori Yoneda MD , Soichiro Kato MD , Keijiro Yamauchi MD , Hirotomo Machiyama MD , Yuki Nishikawa MD , Osamu Morimura MD, PhD , Akito Miyazaki MD , Kiyohide Komuta MD , Kouji Azuma MD , Satoshi Tanaka MD , Toshie Niki MD, PhD , Atsushi Kumanogoh MD, PhD","doi":"10.1016/j.jtocrr.2025.100891","DOIUrl":"10.1016/j.jtocrr.2025.100891","url":null,"abstract":"<div><h3>Introduction</h3><div>Evidence of immune checkpoint inhibitors (ICIs) combined with chemotherapy for older patients with NSCLC is limited. This real-world study compared the efficacy and safety of atezolizumab plus chemotherapy (ACT) with those of pembrolizumab plus chemotherapy (PCT) for older patients with advanced nonsquamous NSCLC.</div></div><div><h3>Methods</h3><div>This multicenter, retrospective study included 288 patients 65 years or older with advanced or recurrent nonsquamous NSCLC who received PCT or ACT as first-line treatment at 13 institutions in Japan. After one-to-one propensity score matching, overall survival (OS), the incidence of grade 3 or higher treatment-related adverse events, and all-grade pneumonitis of the PCT and ACT groups were compared.</div></div><div><h3>Results</h3><div>After propensity score matching, 54 patients were included in each of the groups. OS did not significantly differ between the PCT and ACT groups. The median OS was 16.6 months for both groups. Compared with the PCT group, the ACT group had a hazard ratio of 1.09 (95% confidence interval [CI]: 0.68–1.74; <em>p</em> = 0.7). Grade 3 or higher adverse events occurred in 40.7% and 33.3% of patients in the PCT and ACT groups, respectively (<em>p</em> = 0.55). The incidence of treatment-related pneumonitis of the PCT group was significantly higher (29.6%, including 11 grade ≥3 cases) than that of the ACT group (5.6%, including two grade ≥3 cases) (<em>p</em> = 0.002).</div></div><div><h3>Conclusions</h3><div>ACT may be associated with a more favorable safety profile than that of PCT for the Japanese population; therefore, ACT could be considered a treatment option for older patients with advanced nonsquamous NSCLC.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 11","pages":"Article 100891"},"PeriodicalIF":3.5,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145271077","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 : 2025-08-07DOI: 10.1016/j.jtocrr.2025.100888
Anne-Laurence Le Faou MD, PhD , Dalia Alleaume MSc , Ingrid Allagbé PhD
Background
Limited research exists on sex-specific smoking cessation interventions for patients with lung cancer. This study leverages data from the Consultations de Dépendance Tabagique, the French national database of smoking cessation services (SCS), to identify sex-specific factors influencing smoking cessation in people with lung cancer.
Methods
This retrospective observational study analyzed data from 3407 adults with lung cancer (31.2% women, 68.8% men) registered in the Consultations de Dépendance Tabagique between 2001 and 2018. Participants were people with active tobacco use with at least one follow-up SCS consultation. The primary outcome was 28-day smoking abstinence, confirmed by exhaled carbon monoxide less than 10 parts per million. Multivariate logistic regression identified predictors of abstinence, stratified by sex.
Results
Abstinence rates were similar in women (35.2%) and men (35.4%) (p = 0.40). Women had higher psychological distress (19.8% with depression versus 13.1% in men; p < 0.001) and were more likely to seek SCS independently (19.4% versus 13.6%; p < 0.001). Men smoked more cigarettes daily (27 versus 25; p = 0.002) and had higher alcohol consumption (35.7% versus 13.9%; p < 0.001). Confidence in quitting (women: odds ratio [OR] = 1.91; 95% confidence interval [CI]: 1.27–2.87; men: OR = 1.50; 95% CI: 1.16–1.95) and follow-up consultations (≥7: women: OR = 8.86; 95% CI: 5.69–14.0; men: OR = 6.64; 95% CI: 4.88–9.13) predicted abstinence for both sexes. Among women, hospital referral (OR = 1.63; 95% CI: 1.10–2.43) and living with other persons who smoke (OR = 4.16; 95% CI: 1.70–10.4) increased abstinence, whereas in men, nicotine replacement therapy (OR = 1.46; 95% CI: 1.09–1.97) was beneficial.
Conclusions
The results indicate a need for further research into targeted interventions by sex to evaluate the efficacy of smoking cessation strategies in patients with lung cancer.
{"title":"Predictive Factors for Smoking Cessation Among People With Lung Cancer Attending French Cessation Services, According to Sex","authors":"Anne-Laurence Le Faou MD, PhD , Dalia Alleaume MSc , Ingrid Allagbé PhD","doi":"10.1016/j.jtocrr.2025.100888","DOIUrl":"10.1016/j.jtocrr.2025.100888","url":null,"abstract":"<div><h3>Background</h3><div>Limited research exists on sex-specific smoking cessation interventions for patients with lung cancer. This study leverages data from the Consultations de Dépendance Tabagique, the French national database of smoking cessation services (SCS), to identify sex-specific factors influencing smoking cessation in people with lung cancer.</div></div><div><h3>Methods</h3><div>This retrospective observational study analyzed data from 3407 adults with lung cancer (31.2% women, 68.8% men) registered in the Consultations de Dépendance Tabagique between 2001 and 2018. Participants were people with active tobacco use with at least one follow-up SCS consultation. The primary outcome was 28-day smoking abstinence, confirmed by exhaled carbon monoxide less than 10 parts per million. Multivariate logistic regression identified predictors of abstinence, stratified by sex.</div></div><div><h3>Results</h3><div>Abstinence rates were similar in women (35.2%) and men (35.4%) (<em>p</em> = 0.40). Women had higher psychological distress (19.8% with depression versus 13.1% in men; <em>p</em> < 0.001) and were more likely to seek SCS independently (19.4% versus 13.6%; <em>p</em> < 0.001). Men smoked more cigarettes daily (27 versus 25; <em>p</em> = 0.002) and had higher alcohol consumption (35.7% versus 13.9%; <em>p</em> < 0.001). Confidence in quitting (women: odds ratio [OR] = 1.91; 95% confidence interval [CI]: 1.27–2.87; men: OR = 1.50; 95% CI: 1.16–1.95) and follow-up consultations (≥7: women: OR = 8.86; 95% CI: 5.69–14.0; men: OR = 6.64; 95% CI: 4.88–9.13) predicted abstinence for both sexes. Among women, hospital referral (OR = 1.63; 95% CI: 1.10–2.43) and living with other persons who smoke (OR = 4.16; 95% CI: 1.70–10.4) increased abstinence, whereas in men, nicotine replacement therapy (OR = 1.46; 95% CI: 1.09–1.97) was beneficial.</div></div><div><h3>Conclusions</h3><div>The results indicate a need for further research into targeted interventions by sex to evaluate the efficacy of smoking cessation strategies in patients with lung cancer.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 10","pages":"Article 100888"},"PeriodicalIF":3.5,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145020072","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}
Axl, a receptor tyrosine kinase, is linked to epithelial-mesenchymal transition (EMT). This study aimed to investigate the biologic implications of extracellular domain shedding of phosphorylated Axl (pAxl) in lung adenocarcinoma, focusing on spread through air spaces (STAS) as a potential pathologic representation of EMT.
Methods
This study included 202 patients with resected lung adenocarcinoma. A dual-domain immunohistochemistry approach using separate staining for the extracellular and intracellular domains was used to classify the tumors into shedding and nonshedding pAxl groups. Prognostic analysis was performed using recurrence-free probability (RFP) as the primary outcome. Furthermore, by using a public gene database, we developed the “shedding pAxl score” to experimentally investigate correlations with EMT-related genes.
Results
The shedding pAxl group exhibited significantly worse prognosis than the nonshedding pAxl group (5-year RFP, 54% and 80%, respectively; p < 0.001). This prognostic stratification of pAxl shedding was predominant in STAS-positive patients (5-year RFP, 37% and 75%, p < 0.001), but not in STAS-negative patients (5-year RFP, 73% and 84%, p = 0.3). Multivariate analysis revealed that pathologic stage and pAxl shedding were independent factors for recurrence (hazard ratio 2.28 [1.24–4.91], p = 0.008). The shedding pAxl score correlated strongly with the established EMT signature score (p < 0.001, R = 0.61).
Conclusions
Shedding pAxl has a prognostic impact on lung adenocarcinoma, with a significant effect modification related to STAS. The developed shedding pAxl score, strongly associated with EMT, provides foundational knowledge for further studies on this phenomenon in lung cancer progression.
{"title":"Shedding Phosphorylated Axl Receptor in Lung Adenocarcinoma: Dual-Domain Immunohistochemistry Approach","authors":"Shuji Mishima MD , Takashi Eguchi MD PhD , Yoshinori Sato MD , Shunichiro Matsuoka MD, PhD , Yuichi Oguchi MD , Mari Katsuno MD , Daisuke Nakamura MD , Yukihiro Terada MD , Hirotaka Kumeda MD , Kentaro Miura MD, PhD , Kazutoshi Hamanaka MD, PhD , Mai Iwaya MD, PhD , Takeshi Uehara MD, PhD , Kimihiro Shimizu MD, PhD","doi":"10.1016/j.jtocrr.2025.100889","DOIUrl":"10.1016/j.jtocrr.2025.100889","url":null,"abstract":"<div><h3>Introduction</h3><div>Axl, a receptor tyrosine kinase, is linked to epithelial-mesenchymal transition (EMT). This study aimed to investigate the biologic implications of extracellular domain shedding of phosphorylated Axl (pAxl) in lung adenocarcinoma, focusing on spread through air spaces (STAS) as a potential pathologic representation of EMT.</div></div><div><h3>Methods</h3><div>This study included 202 patients with resected lung adenocarcinoma. A dual-domain immunohistochemistry approach using separate staining for the extracellular and intracellular domains was used to classify the tumors into shedding and nonshedding pAxl groups. Prognostic analysis was performed using recurrence-free probability (RFP) as the primary outcome. Furthermore, by using a public gene database, we developed the “shedding pAxl score” to experimentally investigate correlations with EMT-related genes.</div></div><div><h3>Results</h3><div>The shedding pAxl group exhibited significantly worse prognosis than the nonshedding pAxl group (5-year RFP, 54% and 80%, respectively; <em>p</em> < 0.001). This prognostic stratification of pAxl shedding was predominant in STAS-positive patients (5-year RFP, 37% and 75%, <em>p</em> < 0.001), but not in STAS-negative patients (5-year RFP, 73% and 84%, <em>p</em> = 0.3). Multivariate analysis revealed that pathologic stage and pAxl shedding were independent factors for recurrence (hazard ratio 2.28 [1.24–4.91], <em>p</em> = 0.008). The shedding pAxl score correlated strongly with the established EMT signature score (<em>p</em> < 0.001, R = 0.61).</div></div><div><h3>Conclusions</h3><div>Shedding pAxl has a prognostic impact on lung adenocarcinoma, with a significant effect modification related to STAS. The developed shedding pAxl score, strongly associated with EMT, provides foundational knowledge for further studies on this phenomenon in lung cancer progression.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 10","pages":"Article 100889"},"PeriodicalIF":3.5,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145011006","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 : 2025-08-06DOI: 10.1016/j.jtocrr.2025.100886
Azam Ghafoor MD , Nitin Roper MD , Chul Kim MD, MPH , Chuong D. Hoang MD , Aparna H. Kesarwala MD, PhD , Kevin A. Camphausen MD , Kamran Farouq BS , Elizabeth Akoth RN, BSN, MSN , Corrine Keen RN, BSN, MS , Eva Szabo MD , Hadi Bhageri MD , Arun Rajan MD , Udayan Guha MD, PhD
Introduction
Osimertinib has exhibited impressive efficacy in advanced EGFR-mutated NSCLC; however, resistance is inevitable. We hypothesized that local ablative therapy (LAT) for oligoprogressive disease (up to five sites), followed by osimertinib rechallenge, would be safe and provide additional second progression-free survival (PFS2) benefit.
Methods
This prospective phase 2 trial enrolled EGFR-mutated NSCLC patients in three cohorts: tyrosine kinase inhibitor (TKI)–naive (cohort 1), previously treated with TKI and developed acquired T790M resistance mutation (cohort 2), or previously treated with osimertinib and developed resistance (cohort 3). Patients in cohorts 1 and 2 received upfront osimertinib followed by LAT on oligoprogression, followed by osimertinib rechallenge. Cohort 3 patients underwent LAT on enrollment, followed by osimertinib rechallenge. The primary end points were safety, tolerability, and PFS2 among the patients who underwent LAT across all three cohorts combined. Secondary end points were PFS1 and overall response rates.
Results
A total of 37 patients with EGFR-mutated NSCLC were enrolled; 25 in cohort 1, nine in cohort 2, and three in cohort 3. A total of 21 patients received LAT across all three cohorts combined, yielding a median PFS2 of 3.7 months (95% confidence interval: 1.9–4.6 mo) for this population. A subgroup with exceptionally long PFS2 was identified that achieved lower tumor burden and circulating tumor DNA–negative minimal residual disease of the EGFR clone with osimertinib before undergoing LAT. Most adverse events related to LAT were grades 1 and 2.
Conclusions
This is the first prospective trial exploring local therapy and osimertinib rechallenge on oligoprogression on osimertinib. Interim analysis revealed that PFS2 in the intention-to-treat patients did not meet its primary goal when compared with historical data on continuation of first-generation EGFR TKIs after LAT. However, definite LAT can be carefully considered in patients using circulating tumor DNA–negative minimal residual disease status as a biomarker for predicting who will benefit from continuation of osimertinib post-LAT.
{"title":"Local Ablative Therapy Followed by Osimertinib Rechallenge in Oligoprogressive, EGFR-Mutated NSCLC: A Phase 2 Study","authors":"Azam Ghafoor MD , Nitin Roper MD , Chul Kim MD, MPH , Chuong D. Hoang MD , Aparna H. Kesarwala MD, PhD , Kevin A. Camphausen MD , Kamran Farouq BS , Elizabeth Akoth RN, BSN, MSN , Corrine Keen RN, BSN, MS , Eva Szabo MD , Hadi Bhageri MD , Arun Rajan MD , Udayan Guha MD, PhD","doi":"10.1016/j.jtocrr.2025.100886","DOIUrl":"10.1016/j.jtocrr.2025.100886","url":null,"abstract":"<div><h3>Introduction</h3><div>Osimertinib has exhibited impressive efficacy in advanced EGFR-mutated NSCLC; however, resistance is inevitable. We hypothesized that local ablative therapy (LAT) for oligoprogressive disease (up to five sites), followed by osimertinib rechallenge, would be safe and provide additional second progression-free survival (PFS2) benefit.</div></div><div><h3>Methods</h3><div>This prospective phase 2 trial enrolled <em>EGFR</em>-mutated NSCLC patients in three cohorts: tyrosine kinase inhibitor (TKI)–naive (cohort 1), previously treated with TKI and developed acquired T790M resistance mutation (cohort 2), or previously treated with osimertinib and developed resistance (cohort 3). Patients in cohorts 1 and 2 received upfront osimertinib followed by LAT on oligoprogression, followed by osimertinib rechallenge. Cohort 3 patients underwent LAT on enrollment, followed by osimertinib rechallenge. The primary end points were safety, tolerability, and PFS2 among the patients who underwent LAT across all three cohorts combined. Secondary end points were PFS1 and overall response rates.</div></div><div><h3>Results</h3><div>A total of 37 patients with EGFR-mutated NSCLC were enrolled; 25 in cohort 1, nine in cohort 2, and three in cohort 3. A total of 21 patients received LAT across all three cohorts combined, yielding a median PFS2 of 3.7 months (95% confidence interval: 1.9–4.6 mo) for this population. A subgroup with exceptionally long PFS2 was identified that achieved lower tumor burden and circulating tumor DNA–negative minimal residual disease of the EGFR clone with osimertinib before undergoing LAT. Most adverse events related to LAT were grades 1 and 2.</div></div><div><h3>Conclusions</h3><div>This is the first prospective trial exploring local therapy and osimertinib rechallenge on oligoprogression on osimertinib. Interim analysis revealed that PFS2 in the intention-to-treat patients did not meet its primary goal when compared with historical data on continuation of first-generation EGFR TKIs after LAT. However, definite LAT can be carefully considered in patients using circulating tumor DNA–negative minimal residual disease status as a biomarker for predicting who will benefit from continuation of osimertinib post-LAT.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 10","pages":"Article 100886"},"PeriodicalIF":3.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145096128","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 : 2025-08-06DOI: 10.1016/j.jtocrr.2025.100887
Elvis Obomanu MD , Colton Jones MD , Verna Vanderpuye MD , Nazik Hammad MD
Lung cancer in people of African descent is characterized by transcontinental disparities driven by epidemiologic heterogeneity, systemic inequities, and unequal access to health care. Globally, lung cancer incidence and mortality rates vary; however, underdiagnosis and late-stage presentation in low- and middle-income countries obscure the true prevalence of lung cancer because of limited cancer registries and diagnostic infrastructure. In Africa, most patients with lung cancer present at an advanced stage, primarily because of health illiteracy, misdiagnosis, delayed referrals, and inadequate treatment infrastructure. Although tobacco smoking remains a dominant risk factor worldwide, African populations are disproportionately exposed to environmental and occupational hazards, which substantially elevate their lung cancer risk. In North America, Black people experience disproportionately poor outcomes, including lower rates of lung cancer screening, early diagnosis, surgical intervention, and higher mortality rates compared with their White counterparts. In the Caribbean and South America, Black people continue to face racial infrastructural constraints, racial inequities, and elevated exposure to environmental and occupational carcinogens. Systemic barriers perpetuate these disparities, including limited access to screening, genomic testing, and guideline-concordant therapies.
Achieving equity in lung cancer outcomes requires strategic initiatives, including the expansion of lung cancer registries in Africa, the Caribbean, and South America, to inform evidence-based interventions. Urgent national and international measures focused on prevention and care for populations of African descent, implementing robust tobacco control policies, addressing systemic and racial inequities, and strengthening health care systems to report and manage lung cancer efficiently are essential steps toward reducing disparities. A transcontinental collaborative approach that includes establishing lung cancer research consortia is vital to share best practices in screening protocols, optimize early detection strategies and treatment, and advocate for policy reforms that address the global burden of lung cancer in populations of African descent.
{"title":"Lung Cancer in Patients of African Descent: A Transcontinental Review of Epidemiology, Disparities, Outcomes, and Opportunities for Equity in Africa, North America, South America, and the Caribbean","authors":"Elvis Obomanu MD , Colton Jones MD , Verna Vanderpuye MD , Nazik Hammad MD","doi":"10.1016/j.jtocrr.2025.100887","DOIUrl":"10.1016/j.jtocrr.2025.100887","url":null,"abstract":"<div><div>Lung cancer in people of African descent is characterized by transcontinental disparities driven by epidemiologic heterogeneity, systemic inequities, and unequal access to health care. Globally, lung cancer incidence and mortality rates vary; however, underdiagnosis and late-stage presentation in low- and middle-income countries obscure the true prevalence of lung cancer because of limited cancer registries and diagnostic infrastructure. In Africa, most patients with lung cancer present at an advanced stage, primarily because of health illiteracy, misdiagnosis, delayed referrals, and inadequate treatment infrastructure. Although tobacco smoking remains a dominant risk factor worldwide, African populations are disproportionately exposed to environmental and occupational hazards, which substantially elevate their lung cancer risk. In North America, Black people experience disproportionately poor outcomes, including lower rates of lung cancer screening, early diagnosis, surgical intervention, and higher mortality rates compared with their White counterparts. In the Caribbean and South America, Black people continue to face racial infrastructural constraints, racial inequities, and elevated exposure to environmental and occupational carcinogens. Systemic barriers perpetuate these disparities, including limited access to screening, genomic testing, and guideline-concordant therapies.</div><div>Achieving equity in lung cancer outcomes requires strategic initiatives, including the expansion of lung cancer registries in Africa, the Caribbean, and South America, to inform evidence-based interventions. Urgent national and international measures focused on prevention and care for populations of African descent, implementing robust tobacco control policies, addressing systemic and racial inequities, and strengthening health care systems to report and manage lung cancer efficiently are essential steps toward reducing disparities. A transcontinental collaborative approach that includes establishing lung cancer research consortia is vital to share best practices in screening protocols, optimize early detection strategies and treatment, and advocate for policy reforms that address the global burden of lung cancer in populations of African descent.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 10","pages":"Article 100887"},"PeriodicalIF":3.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145096130","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 : 2025-08-05DOI: 10.1016/j.jtocrr.2025.100885
Zhuomiao Ye MD , Xin Li PhD , Minghui Zhang PhD , Fei Xie MD , Xiangwen Luo MSc , Chao Deng MD , Dan Yang MSc , Mingzhu Yin PhD
NUT carcinoma is a rare and highly aggressive malignancy characterized by rapid progression, resistance to conventional therapies, and an extremely poor prognosis. This report presents a 36-year-old patient with stage IIIB primary pulmonary NUT carcinoma who achieved remarkable clinical outcomes with NHWD-870 monotherapy, a novel BET inhibitor. After just 1 month of treatment, imaging revealed a partial response, and a complete response was achieved within 5 months. Postoperative pathologic examination confirmed no residual cancer cells, and the patient has remained disease-free without recurrence or metastasis to date. To explore the underlying mechanisms of this therapeutic response, single-cell RNA sequencing was performed on the tumor tissue, revealing enhanced activity of immune cells, particularly effector CD8+ T-cells, within the tumor microenvironment. This suggests that NHWD-870 exerts its effects through both direct tumor suppression and modulation of the immune microenvironment. This case highlights the exceptional efficacy of BET inhibitors in the treatment of NUT carcinoma, as evidenced by the first report of complete response achieved with BET inhibitor monotherapy, and supports their potential as a personalized therapeutic strategy.
{"title":"Complete Response to BET Inhibitor in Primary Pulmonary NUT Carcinoma With Single-Cell Sequencing-Based Analysis: A Case Report","authors":"Zhuomiao Ye MD , Xin Li PhD , Minghui Zhang PhD , Fei Xie MD , Xiangwen Luo MSc , Chao Deng MD , Dan Yang MSc , Mingzhu Yin PhD","doi":"10.1016/j.jtocrr.2025.100885","DOIUrl":"10.1016/j.jtocrr.2025.100885","url":null,"abstract":"<div><div>NUT carcinoma is a rare and highly aggressive malignancy characterized by rapid progression, resistance to conventional therapies, and an extremely poor prognosis. This report presents a 36-year-old patient with stage IIIB primary pulmonary NUT carcinoma who achieved remarkable clinical outcomes with NHWD-870 monotherapy, a novel BET inhibitor. After just 1 month of treatment, imaging revealed a partial response, and a complete response was achieved within 5 months. Postoperative pathologic examination confirmed no residual cancer cells, and the patient has remained disease-free without recurrence or metastasis to date. To explore the underlying mechanisms of this therapeutic response, single-cell RNA sequencing was performed on the tumor tissue, revealing enhanced activity of immune cells, particularly effector CD8+ T-cells, within the tumor microenvironment. This suggests that NHWD-870 exerts its effects through both direct tumor suppression and modulation of the immune microenvironment. This case highlights the exceptional efficacy of BET inhibitors in the treatment of NUT carcinoma, as evidenced by the first report of complete response achieved with BET inhibitor monotherapy, and supports their potential as a personalized therapeutic strategy.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 10","pages":"Article 100885"},"PeriodicalIF":3.5,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144919985","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 : 2025-08-05DOI: 10.1016/j.jtocrr.2025.100884
Byoung Chul Cho MD, PhD , Myung-Ju Ahn MD , Makoto Nishio MD , Haruyasu Murakami MD , Dong Wan-Kim MD , Sang-We Kim MD , Sana D. Karam MD , Ana Estival PhD , Chia-Chi Lin MD, PhD , Jose Manuel Trigo MD , Rosa Alvarez MD , Chih Liang Wang MD , Mingchao Xie PhD , Sonia Iyer PhD , Jon Armstrong MSc , Priti Chugh PhD , Haiyi Jiang MD , Julie E. Bauman MD
Introduction
The phase 1 CLOVER study (NCT03509012) evaluated durvalumab with or without tremelimumab in combination with concurrent chemoradiotherapy (cCRT) in patients with advanced solid tumors; here, we report findings from the limited-stage SCLC (LS-SCLC) cohort.
Methods
Patients with pathologically confirmed LS-SCLC whose disease could be encompassed within a radical radiation portal received durvalumab (arms 1 and 2) or durvalumab plus tremelimumab (arms 3 and 4) in combination with cCRT (cisplatin-etoposide and either standard radiotherapy [arms 1 and 3] or hyperfractionated radiotherapy [arms 2 and 4]). The primary end point was safety and tolerability. Preliminary efficacy and candidate biomarkers of response were assessed.
Results
Overall, 33 patients were enrolled: 12 in arm 1, 12 in arm 2, six in arm 3, and three in arm 4. No patients had dose-limiting toxicity. Grade 3 or 4 adverse events occurred in 79.2% of patients from arms 1 and 2 and 88.9% from arms 3 and 4; the most common were hematologic events. In arms 1, 2, 3, and 4, objective response rate was 66.7%, 66.7%, 83.3%, and 100.0%, disease control rate was 90.9%, 100.0%, 100.0%, and 100.0% at 18 weeks and 72.7%, 83.3%, 100.0%, and 100.0% at 48 weeks, and the median progression-free survival (PFS) (95% confidence interval) was 9.2 months (5.3‒not estimable [NE]), 16.6 months (8.4–NE), not reached (16.6–NE), and 9.3 months (6.3–NE), respectively. In exploratory biomarker analyses, no difference in PFS by programmed cell death-ligand 1 expression level was observed; median PFS was numerically greater in high versus low tumor inflammation signature and CD8A expression subgroups.
Conclusions
Durvalumab in combination with cCRT, with or without tremelimumab, was tolerable and active in patients with LS-SCLC.
{"title":"Durvalumab With or Without Tremelimumab in Combination With Chemoradiotherapy in Patients With Limited-Stage SCLC: Results from the Phase 1 CLOVER Study","authors":"Byoung Chul Cho MD, PhD , Myung-Ju Ahn MD , Makoto Nishio MD , Haruyasu Murakami MD , Dong Wan-Kim MD , Sang-We Kim MD , Sana D. Karam MD , Ana Estival PhD , Chia-Chi Lin MD, PhD , Jose Manuel Trigo MD , Rosa Alvarez MD , Chih Liang Wang MD , Mingchao Xie PhD , Sonia Iyer PhD , Jon Armstrong MSc , Priti Chugh PhD , Haiyi Jiang MD , Julie E. Bauman MD","doi":"10.1016/j.jtocrr.2025.100884","DOIUrl":"10.1016/j.jtocrr.2025.100884","url":null,"abstract":"<div><h3>Introduction</h3><div>The phase 1 CLOVER study (NCT03509012) evaluated durvalumab with or without tremelimumab in combination with concurrent chemoradiotherapy (cCRT) in patients with advanced solid tumors; here, we report findings from the limited-stage SCLC (LS-SCLC) cohort.</div></div><div><h3>Methods</h3><div>Patients with pathologically confirmed LS-SCLC whose disease could be encompassed within a radical radiation portal received durvalumab (arms 1 and 2) or durvalumab plus tremelimumab (arms 3 and 4) in combination with cCRT (cisplatin-etoposide and either standard radiotherapy [arms 1 and 3] or hyperfractionated radiotherapy [arms 2 and 4]). The primary end point was safety and tolerability. Preliminary efficacy and candidate biomarkers of response were assessed.</div></div><div><h3>Results</h3><div>Overall, 33 patients were enrolled: 12 in arm 1, 12 in arm 2, six in arm 3, and three in arm 4. No patients had dose-limiting toxicity. Grade 3 or 4 adverse events occurred in 79.2% of patients from arms 1 and 2 and 88.9% from arms 3 and 4; the most common were hematologic events. In arms 1, 2, 3, and 4, objective response rate was 66.7%, 66.7%, 83.3%, and 100.0%, disease control rate was 90.9%, 100.0%, 100.0%, and 100.0% at 18 weeks and 72.7%, 83.3%, 100.0%, and 100.0% at 48 weeks, and the median progression-free survival (PFS) (95% confidence interval) was 9.2 months (5.3‒not estimable [NE]), 16.6 months (8.4–NE), not reached (16.6–NE), and 9.3 months (6.3–NE), respectively. In exploratory biomarker analyses, no difference in PFS by programmed cell death-ligand 1 expression level was observed; median PFS was numerically greater in high versus low tumor inflammation signature and <em>CD8A</em> expression subgroups.</div></div><div><h3>Conclusions</h3><div>Durvalumab in combination with cCRT, with or without tremelimumab, was tolerable and active in patients with LS-SCLC.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 10","pages":"Article 100884"},"PeriodicalIF":3.5,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155158","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}
For patients with oncogene-addicted NSCLC treated with tyrosine kinase inhibitors (TKIs), weight gain has recently gained attention as a frequent treatment-related effect. Identifying those TKIs more frequently associated with weight gain is crucial for further characterizing body composition-related modifications, deepening their metabolic impact, and guiding treatment decisions, considering the potential influence of weight gain on patients' quality of life and long-term outcomes.
Methods
A systematic search was conducted across PubMed, Scopus, Cochrane, and meeting resources. A meta-analysis was conducted to quantify the magnitude of weight gain, and meta-regression was applied to explore the association between this side effect, and demographic and clinical parameters.
Results
Among 7596 identified studies from January 2009 to December 2024, 18 pivotal trials reporting weight gain data were included in the final analysis, encompassing a total of 25 arms. Lorlatinib revealed the highest risk of treatment-induced weight gain [incidence 36%; 95% confidence interval (CI): 26%–46%; I2 = 92%], followed by alectinib [incidence 15%; 95% CI: 12%–18%; I2 = 52%] and crizotinib [incidence 5%; 95% CI: 0%–13%; I2 = 93%]. Osimertinib and erlotinib indicated the lowest incidence of weight gain. The meta-regression revealed no significant correlation among weight gain, sex, age, and performance status, thus suggesting a drug-specific effect.
Conclusions
Our findings confirmed the unique profile of lorlatinib regarding weight gain, regardless of patient characteristics. Considering the impressive prognostic horizons achievable with TKIs in oncogene-addicted NSCLC, adequate reporting in clinical trials, assessment and monitoring of weight gain, body composition modifications, and impact on quality of life should be prioritized, together with adequate lifestyle-based strategies for its management.
{"title":"Meta-Analysis Exploring Tyrosine Kinase Inhibitor-Induced Weight Gain in Oncogene-Addicted NSCLC","authors":"Ilaria Mariangela Scaglione MD , Alice Avancini PhD , Serena Eccher MD , Anita Borsati MSc , Luca Pasqualin MD , Giulia La Cava MD , Ilaria Trestini RD , Daniela Tregnago PhD , Marco Sposito MD , Jessica Insolda MSc , Diana Giannarelli PhD , Michele Milella MD , Sara Pilotto PhD , Lorenzo Belluomini PhD","doi":"10.1016/j.jtocrr.2025.100881","DOIUrl":"10.1016/j.jtocrr.2025.100881","url":null,"abstract":"<div><h3>Background</h3><div>For patients with oncogene-addicted NSCLC treated with tyrosine kinase inhibitors (TKIs), weight gain has recently gained attention as a frequent treatment-related effect. Identifying those TKIs more frequently associated with weight gain is crucial for further characterizing body composition-related modifications, deepening their metabolic impact, and guiding treatment decisions, considering the potential influence of weight gain on patients' quality of life and long-term outcomes.</div></div><div><h3>Methods</h3><div>A systematic search was conducted across PubMed, Scopus, Cochrane, and meeting resources. A meta-analysis was conducted to quantify the magnitude of weight gain, and meta-regression was applied to explore the association between this side effect, and demographic and clinical parameters.</div></div><div><h3>Results</h3><div>Among 7596 identified studies from January 2009 to December 2024, 18 pivotal trials reporting weight gain data were included in the final analysis, encompassing a total of 25 arms. Lorlatinib revealed the highest risk of treatment-induced weight gain [incidence 36%; 95% confidence interval (CI): 26%–46%; I<sup>2</sup> = 92%], followed by alectinib [incidence 15%; 95% CI: 12%–18%; I<sup>2</sup> = 52%] and crizotinib [incidence 5%; 95% CI: 0%–13%; I<sup>2</sup> = 93%]. Osimertinib and erlotinib indicated the lowest incidence of weight gain. The meta-regression revealed no significant correlation among weight gain, sex, age, and performance status, thus suggesting a drug-specific effect.</div></div><div><h3>Conclusions</h3><div>Our findings confirmed the unique profile of lorlatinib regarding weight gain, regardless of patient characteristics. Considering the impressive prognostic horizons achievable with TKIs in oncogene-addicted NSCLC, adequate reporting in clinical trials, assessment and monitoring of weight gain, body composition modifications, and impact on quality of life should be prioritized, together with adequate lifestyle-based strategies for its management.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 10","pages":"Article 100881"},"PeriodicalIF":3.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144922421","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 : 2025-07-17DOI: 10.1016/j.jtocrr.2025.100880
Ella A. Eklund MD , Sama I. Sayin MD, PhD , Jonas Smith Jonsson MD , Hannes van Renswoude MD , Jan Nyman MD, PhD , Andreas Hallqvist MD, PhD , Clotilde Wiel PhD , Volkan I. Sayin PhD
<div><h3>Introduction</h3><div>Immune checkpoint blockade (ICB) is a standard first-line treatment for stage IV NSCLC without actionable oncogenic alterations. <em>KRAS</em> mutations, prevalent in 30% to 40% lung adenocarcinomas (LUAD) in Western populations, currently lack targeted first-line therapies. This study aimed to assess the predictive value of <em>KRAS</em> mutations for clinical outcomes after distinct ICB regimens, validating our previous findings in a larger cohort with extended follow-up.</div></div><div><h3>Methods</h3><div>We conducted a retrospective multicenter study including consecutive stage IV LUAD patients (n = 424) treated with either ICB or platinum-doublet chemotherapy between 2016 and 2021 in Western Sweden. Patient demographics, tumor characteristics, treatment details, and survival outcomes were retrospectively collected from patient charts and the Swedish National Lung Cancer Registry. <em>KRAS</em> mutational status was assessed by next-generation sequencing. Primary end points included overall survival (OS) and progression-free survival (PFS), analyzed using Kaplan-Meier curves and multivariate Cox regression.</div></div><div><h3>Results</h3><div>Among 424 patients diagnosed with metastatic LUAD, 40% harbored <em>KRAS</em> mutations (<em>KRAS</em><sup>MUT</sup>). <em>KRAS</em><sup>MUT</sup> patients exhibited significant improvement in OS (16 versus 8 mo, <em>p</em> < 0.001) and PFS (8 mo versus 5 mo, <em>p</em> < 0.001) with ICB monotherapy. In contrast, <em>KRAS</em> wild-type (<em>KRAS</em><sup>WT</sup>) patients derived no survival advantage from ICB monotherapy (OS, 8 mo versus 8 mo, <em>p</em> = 0.648; PFS 4 mo versus 5 mo, <em>p</em> = 0.871) although they did so with chemoimmunotherapy (OS, 15 mo versus 8 mo, <em>p</em> = 0.032; PFS, 6 mo vs 5 mo, <em>p</em> = 0.033). On multivariate analysis, monotherapy was confirmed as an independent factor improving outcomes in KRAS-mutated patients (hazard ratio [HR] 0.533, 95% confidence interval 0.311-0.912, <em>p</em> = 0.018). Finally, we identified <em>KRAS</em><sup>G12C</sup> (OS: 13.7 mo versus 10.5 mo, <em>p</em> = 0.0046, PFS: 7.7 mo versus 6.2 mo, <em>p</em> = 0.002) and <em>KRAS</em><sup>G12V</sup> (OS: 24.2 mo versus 7.2 mo, <em>p</em> = 0.0204; PFS: 13.7 mo versus 4.5 mo, <em>p</em> = 0.063) but not <em>KRAS</em><sup>G12D</sup> (OS, 5.8 mo versus 6.2 mo, <em>p</em> = 0.777; PFS, 4.6 mo versus 3.2 mo, <em>p</em> = 0.694) as distinctly and independently predictive of improved survival after receiving ICB-containing treatment.</div></div><div><h3>Conclusions</h3><div><em>KRAS</em> mutations predict substantial and sustained clinical benefit from first-line ICB monotherapy in metastatic LUAD, whereas <em>KRAS</em> wild-type patients do not. <em>KRAS</em><sup>G12C</sup> and <em>KRAS</em><sup>G12V</sup> mutations confer improved survival, whereas <em>KRAS</em><sup>G12D</sup> does not. Integrating <em>KRAS</em> mutation status into clinical practice could
{"title":"Monotherapy With Immune Checkpoint Blockade Improves Survival Outcomes in KRAS-Mutant but Not KRAS Wild-Type Metastatic Lung Adenocarcinoma: Validation From an Extended Swedish Cohort","authors":"Ella A. Eklund MD , Sama I. Sayin MD, PhD , Jonas Smith Jonsson MD , Hannes van Renswoude MD , Jan Nyman MD, PhD , Andreas Hallqvist MD, PhD , Clotilde Wiel PhD , Volkan I. Sayin PhD","doi":"10.1016/j.jtocrr.2025.100880","DOIUrl":"10.1016/j.jtocrr.2025.100880","url":null,"abstract":"<div><h3>Introduction</h3><div>Immune checkpoint blockade (ICB) is a standard first-line treatment for stage IV NSCLC without actionable oncogenic alterations. <em>KRAS</em> mutations, prevalent in 30% to 40% lung adenocarcinomas (LUAD) in Western populations, currently lack targeted first-line therapies. This study aimed to assess the predictive value of <em>KRAS</em> mutations for clinical outcomes after distinct ICB regimens, validating our previous findings in a larger cohort with extended follow-up.</div></div><div><h3>Methods</h3><div>We conducted a retrospective multicenter study including consecutive stage IV LUAD patients (n = 424) treated with either ICB or platinum-doublet chemotherapy between 2016 and 2021 in Western Sweden. Patient demographics, tumor characteristics, treatment details, and survival outcomes were retrospectively collected from patient charts and the Swedish National Lung Cancer Registry. <em>KRAS</em> mutational status was assessed by next-generation sequencing. Primary end points included overall survival (OS) and progression-free survival (PFS), analyzed using Kaplan-Meier curves and multivariate Cox regression.</div></div><div><h3>Results</h3><div>Among 424 patients diagnosed with metastatic LUAD, 40% harbored <em>KRAS</em> mutations (<em>KRAS</em><sup>MUT</sup>). <em>KRAS</em><sup>MUT</sup> patients exhibited significant improvement in OS (16 versus 8 mo, <em>p</em> < 0.001) and PFS (8 mo versus 5 mo, <em>p</em> < 0.001) with ICB monotherapy. In contrast, <em>KRAS</em> wild-type (<em>KRAS</em><sup>WT</sup>) patients derived no survival advantage from ICB monotherapy (OS, 8 mo versus 8 mo, <em>p</em> = 0.648; PFS 4 mo versus 5 mo, <em>p</em> = 0.871) although they did so with chemoimmunotherapy (OS, 15 mo versus 8 mo, <em>p</em> = 0.032; PFS, 6 mo vs 5 mo, <em>p</em> = 0.033). On multivariate analysis, monotherapy was confirmed as an independent factor improving outcomes in KRAS-mutated patients (hazard ratio [HR] 0.533, 95% confidence interval 0.311-0.912, <em>p</em> = 0.018). Finally, we identified <em>KRAS</em><sup>G12C</sup> (OS: 13.7 mo versus 10.5 mo, <em>p</em> = 0.0046, PFS: 7.7 mo versus 6.2 mo, <em>p</em> = 0.002) and <em>KRAS</em><sup>G12V</sup> (OS: 24.2 mo versus 7.2 mo, <em>p</em> = 0.0204; PFS: 13.7 mo versus 4.5 mo, <em>p</em> = 0.063) but not <em>KRAS</em><sup>G12D</sup> (OS, 5.8 mo versus 6.2 mo, <em>p</em> = 0.777; PFS, 4.6 mo versus 3.2 mo, <em>p</em> = 0.694) as distinctly and independently predictive of improved survival after receiving ICB-containing treatment.</div></div><div><h3>Conclusions</h3><div><em>KRAS</em> mutations predict substantial and sustained clinical benefit from first-line ICB monotherapy in metastatic LUAD, whereas <em>KRAS</em> wild-type patients do not. <em>KRAS</em><sup>G12C</sup> and <em>KRAS</em><sup>G12V</sup> mutations confer improved survival, whereas <em>KRAS</em><sup>G12D</sup> does not. Integrating <em>KRAS</em> mutation status into clinical practice could","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 10","pages":"Article 100880"},"PeriodicalIF":3.5,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144920070","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 : 2025-07-10DOI: 10.1016/j.jtocrr.2025.100877
Iris van 't Erve PhD , Isabelle Blanchard BS , Judy Y. Pagtama MSN , Alison J. Holmes Tisch MSN , Ash A. Alizadeh MD, PhD , Kavitha Ramchandran MD , Heather A. Wakelee MD , Sukhmani K. Padda MD , Maximilian Diehn MD, PhD , Joel W. Neal MD, PhD
Immune checkpoint inhibitors provide clinical benefit to a subset of patients with metastatic NSCLC, yet the reliable prediction of long-term outcomes remains challenging. We conducted a prospective phase 2 clinical trial to evaluate circulating tumor DNA (ctDNA) as a surrogate biomarker for early clinical response to pembrolizumab monotherapy (NCT02955758). Tumor-informed targeted sequencing of pretreatment and early on-treatment plasma ctDNA in 25 patients with metastatic NSCLC was performed. On-treatment ctDNA response, defined as at least a threefold ctDNA variant allele frequency decrease after three cycles of pembrolizumab versus baseline, was able to predict with 100%, 66%, and 100% accuracy partial response, stable disease, and progressive disease radiologic response, respectively. Molecular response was also correlated with progression-free survival. This study confirms the potential clinical utility of early on-treatment ctDNA-based response evaluation in patients treated with immune checkpoint inhibitors, creating the opportunity for early treatment intervention in nonresponders.
{"title":"Brief Report: Prospective Trial of Pembrolizumab Monotherapy in Metastatic NSCLC Evaluating Circulating Tumor DNA as a Surrogate Biomarker of Response","authors":"Iris van 't Erve PhD , Isabelle Blanchard BS , Judy Y. Pagtama MSN , Alison J. Holmes Tisch MSN , Ash A. Alizadeh MD, PhD , Kavitha Ramchandran MD , Heather A. Wakelee MD , Sukhmani K. Padda MD , Maximilian Diehn MD, PhD , Joel W. Neal MD, PhD","doi":"10.1016/j.jtocrr.2025.100877","DOIUrl":"10.1016/j.jtocrr.2025.100877","url":null,"abstract":"<div><div>Immune checkpoint inhibitors provide clinical benefit to a subset of patients with metastatic NSCLC, yet the reliable prediction of long-term outcomes remains challenging. We conducted a prospective phase 2 clinical trial to evaluate circulating tumor DNA (ctDNA) as a surrogate biomarker for early clinical response to pembrolizumab monotherapy (NCT02955758). Tumor-informed targeted sequencing of pretreatment and early on-treatment plasma ctDNA in 25 patients with metastatic NSCLC was performed. On-treatment ctDNA response, defined as at least a threefold ctDNA variant allele frequency decrease after three cycles of pembrolizumab versus baseline, was able to predict with 100%, 66%, and 100% accuracy partial response, stable disease, and progressive disease radiologic response, respectively. Molecular response was also correlated with progression-free survival. This study confirms the potential clinical utility of early on-treatment ctDNA-based response evaluation in patients treated with immune checkpoint inhibitors, creating the opportunity for early treatment intervention in nonresponders.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 9","pages":"Article 100877"},"PeriodicalIF":3.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144879600","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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