Pub Date : 2025-11-01DOI: 10.1016/j.jtocrr.2025.100876
Kai-Lin Liu BA, BS , Alex Watts MS , Connor B. Grady MPH , Geoffrey Liu MD, MSc , Devalben Patel BSc, MLT , Karmugi Balaratnam MD , Stephen V. Liu MD , Gabriela Bravo Montenegro MD , Yunan Nie MD , Jorge Nieva MD , Amanda Herrmann MD , Kristen Marrone MD , Vincent Lam MD , Fangdi Sun MD , Jonathan Dowell MD , William Schwartzman MD , Vamsidhar Velcheti MD , Olivia Fankuchen MD, MS , Tasfiq Ullah MD , Liza Villaruz MD , Melina E. Marmarelis MD, MSCE
Introduction
The prognostic significance of baseline and on-treatment brain and liver metastasis in ALK+ or ROS1+ metastatic NSCLC (mNSCLC) remains unclear. As we consider intensification strategies, it is critical to identify factors that predict high-risk disease.
Methods
Clinical characteristics and outcomes were abstracted from the electronic medical records of patients with ALK+ or ROS1+ mNSCLC. Baseline characteristics and the cumulative incidence (CI) of brain and liver metastases were compared (≥2-year survivors versus <2-year; pre-2017 versus post-2017). Multivariable Cox proportional hazard models were used to evaluate the association between factors and overall survival, and multivariable logistic regression models were used for the odds of death within 2 years.
Results
A total of 310 patients with ALK+ mNSCLC were identified (≥2-y: 229, <2-y: 81). There was no difference in cumulative incidence of brain metastases between survival groups (29% at 21 mo). However, the cumulative incidence of liver metastasis was higher in those who survived less than 2 years (20.9% versus 5.4% at 21 mo). The cumulative incidence of brain but not liver metastases has improved post-2017 with the newer generation of ALK tyrosine kinase inhibitors. There were 69 patients with ROS1+ mNSCLC who were identified (≥2-y: 46, < 2-y: 23). There was no significant difference in the cumulative incidence of brain or liver metastases between less-than-2-year and greater-than-or-equal-to-2-year survivor cohorts (p = 0.664, p = 0.201).
Conclusions
Among patients with ALK+ but not ROS1+ mNSCLC, the presence of liver metastases at baseline and on-treatment was associated with worse survival. In the ALK+ population, the cumulative incidence of brain but not liver metastases is improving, highlighting a need for therapies effective at the treatment and prevention of liver metastases.
{"title":"Characteristics of Short-Term Survivors With ALK or ROS1-Altered Metastatic NSCLC","authors":"Kai-Lin Liu BA, BS , Alex Watts MS , Connor B. Grady MPH , Geoffrey Liu MD, MSc , Devalben Patel BSc, MLT , Karmugi Balaratnam MD , Stephen V. Liu MD , Gabriela Bravo Montenegro MD , Yunan Nie MD , Jorge Nieva MD , Amanda Herrmann MD , Kristen Marrone MD , Vincent Lam MD , Fangdi Sun MD , Jonathan Dowell MD , William Schwartzman MD , Vamsidhar Velcheti MD , Olivia Fankuchen MD, MS , Tasfiq Ullah MD , Liza Villaruz MD , Melina E. Marmarelis MD, MSCE","doi":"10.1016/j.jtocrr.2025.100876","DOIUrl":"10.1016/j.jtocrr.2025.100876","url":null,"abstract":"<div><h3>Introduction</h3><div>The prognostic significance of baseline and on-treatment brain and liver metastasis in <em>ALK</em>+ or <em>ROS1</em>+ metastatic NSCLC (mNSCLC) remains unclear. As we consider intensification strategies, it is critical to identify factors that predict high-risk disease.</div></div><div><h3>Methods</h3><div>Clinical characteristics and outcomes were abstracted from the electronic medical records of patients with <em>ALK</em>+ or <em>ROS1</em>+ mNSCLC. Baseline characteristics and the cumulative incidence (CI) of brain and liver metastases were compared (≥2-year survivors versus <2-year; pre-2017 versus post-2017). Multivariable Cox proportional hazard models were used to evaluate the association between factors and overall survival, and multivariable logistic regression models were used for the odds of death within 2 years.</div></div><div><h3>Results</h3><div>A total of 310 patients with <em>ALK</em>+ mNSCLC were identified (≥2-y: 229, <2-y: 81). There was no difference in cumulative incidence of brain metastases between survival groups (29% at 21 mo). However, the cumulative incidence of liver metastasis was higher in those who survived less than 2 years (20.9% versus 5.4% at 21 mo). The cumulative incidence of brain but not liver metastases has improved post-2017 with the newer generation of ALK tyrosine kinase inhibitors. There were 69 patients with <em>ROS1</em>+ mNSCLC who were identified (≥2-y: 46, < 2-y: 23). There was no significant difference in the cumulative incidence of brain or liver metastases between less-than-2-year and greater-than-or-equal-to-2-year survivor cohorts (<em>p</em> = 0.664, <em>p</em> = 0.201).</div></div><div><h3>Conclusions</h3><div>Among patients with <em>ALK</em>+ but not <em>ROS1</em>+ mNSCLC, the presence of liver metastases at baseline and on-treatment was associated with worse survival. In the ALK+ population, the cumulative incidence of brain but not liver metastases is improving, highlighting a need for therapies effective at the treatment and prevention of liver metastases.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 11","pages":"Article 100876"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145425161","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 : 2025-11-01DOI: 10.1016/j.jtocrr.2025.100911
Youling Gong MD , Qingsong Pang MD , Rong Yu MD , Zhengfei Zhu MD , Jiangqiong Huang MD , Yufeng Cheng MD , Diansheng Zhong MD , Hongbo Wu MD , Seung Soo Yoo PhD , Tracy Dobbs MD , Zinan Bao MD , Yunxia Zuo MD , Yujuan Gao PhD , Pu Sun PhD , You Lu MD
Introduction
Patients with limited-stage SCLC (LS-SCLC) have a substantial unmet clinical need for new treatments that delay disease progression and prolong survival.
Methods
In this phase 2, multicenter, randomized, multiarm, open-label trial, patients with untreated LS-SCLC received ociperlimab and tislelizumab plus concurrent chemoradiotherapy (cCRT) (arm A), tislelizumab plus cCRT (arm B), or cCRT (arm C). The primary objective was to compare progression-free survival (PFS) per investigator for arms A and B versus C (NCT04952597). The contribution of ociperlimab was explored by comparison of arms A versus B. Statistical analyses were descriptive, with no formal hypothesis testing.
Results
A total of 126 patients were randomized to arms A (N = 41), B (N = 42), and C (N = 43). The median PFS [95% confidence interval] exhibited a trend for improvement in arms A (12.6 [8.7–not estimable] months) and B (13.2 [8.5–not estimable]) compared with C (9.5 [8.3–14.4]); the PFS benefit was comparable between Arms A and B.
The objective response rate, complete response rate, and median duration of response were numerically higher in arms A and B than in C. The median overall survival was not reached in all three arms, and the median distant metastasis–free survival revealed no trend for improvement for arms A and B compared with C. All patients experienced at least one treatment-related treatment-emergent adverse event.
Conclusions
Ociperlimab and tislelizumab plus cCRT and tislelizumab plus cCRT exhibited a trend for improvement in PFS and numerically higher objective response rate compared with cCRT, with no new safety signals beyond the known profiles of immune checkpoint inhibitors and cCRT. Adding ociperlimab to tislelizumab plus cCRT was not associated with additional improvement in efficacy.
{"title":"AdvanTIG-204: A Phase 2, Randomized, Open-Label Study of Ociperlimab Plus Tislelizumab and Concurrent Chemoradiotherapy Versus Tislelizumab and Concurrent Chemotherapy Versus Concurrent Chemoradiotherapy in First-Line Limited-Stage SCLC","authors":"Youling Gong MD , Qingsong Pang MD , Rong Yu MD , Zhengfei Zhu MD , Jiangqiong Huang MD , Yufeng Cheng MD , Diansheng Zhong MD , Hongbo Wu MD , Seung Soo Yoo PhD , Tracy Dobbs MD , Zinan Bao MD , Yunxia Zuo MD , Yujuan Gao PhD , Pu Sun PhD , You Lu MD","doi":"10.1016/j.jtocrr.2025.100911","DOIUrl":"10.1016/j.jtocrr.2025.100911","url":null,"abstract":"<div><h3>Introduction</h3><div>Patients with limited-stage SCLC (LS-SCLC) have a substantial unmet clinical need for new treatments that delay disease progression and prolong survival.</div></div><div><h3>Methods</h3><div>In this phase 2, multicenter, randomized, multiarm, open-label trial, patients with untreated LS-SCLC received ociperlimab and tislelizumab plus concurrent chemoradiotherapy (cCRT) (arm A), tislelizumab plus cCRT (arm B), or cCRT (arm C). The primary objective was to compare progression-free survival (PFS) per investigator for arms A and B versus C (NCT04952597). The contribution of ociperlimab was explored by comparison of arms A versus B. Statistical analyses were descriptive, with no formal hypothesis testing.</div></div><div><h3>Results</h3><div>A total of 126 patients were randomized to arms A (N = 41), B (N = 42), and C (N = 43). The median PFS [95% confidence interval] exhibited a trend for improvement in arms A (12.6 [8.7–not estimable] months) and B (13.2 [8.5–not estimable]) compared with C (9.5 [8.3–14.4]); the PFS benefit was comparable between Arms A and B.</div><div>The objective response rate, complete response rate, and median duration of response were numerically higher in arms A and B than in C. The median overall survival was not reached in all three arms, and the median distant metastasis–free survival revealed no trend for improvement for arms A and B compared with C. All patients experienced at least one treatment-related treatment-emergent adverse event.</div></div><div><h3>Conclusions</h3><div>Ociperlimab and tislelizumab plus cCRT and tislelizumab plus cCRT exhibited a trend for improvement in PFS and numerically higher objective response rate compared with cCRT, with no new safety signals beyond the known profiles of immune checkpoint inhibitors and cCRT. Adding ociperlimab to tislelizumab plus cCRT was not associated with additional improvement in efficacy.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 11","pages":"Article 100911"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145425159","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 : 2025-11-01DOI: 10.1016/j.jtocrr.2025.100875
Sanjana Mullangi MD , Manidhar Reddy Lekkala MD , Sarah Blocker PharmD , Diana Kim PharmD , Jun Zhang MD , Chao Huang MD , Prakash Neupane MD , Haoran Li MD , Timothy Schieber PharmD
Introduction
SCLC remains the most aggressive lung cancer with a poor prognosis. Tarlatamab, a bispecific T-cell engager, is approved for use in extensive-stage SCLC after progression on a platinum-based chemotherapy on the basis of the DeLLphi-301 trial. Because of the restrictive inclusion criteria of this trial, substantial gaps remain in our understanding of treatment for many patients.
Methods
We performed a retrospective chart review of patients who were treated with tarlatamab at the University of Kansas Cancer Center from May 2024 through December 2024 for SCLC (cohort 1) or extrapulmonary small cell carcinoma (EPSCC) (cohort 2). Patients were included if they received at least one dose of tarlatamab regardless of baseline characteristics.
Results
A total of 21 patients were included in cohort 1, and three patients were included in cohort 2. In the SCLC cohort, 14 patients (66.6%) had central nervous system (CNS) involvement, five patients (23.8%) required baseline oxygen, and five patients (23.8%) had an Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or greater. There were 13 patients (61.9%) who developed cytokine release syndrome (CRS), with grade 3 or higher CRS noted in two patients (15.3%). There were 10 patients (47.6%) who developed immune effector cell–associated neurotoxicity syndrome (ICANS), with three patients (14.2%) developing grade 3 or higher ICANS. In the three patients with extrapulmonary small cell carcinoma, any-grade CRS occurred in two patients (66.7%), and grade 1 ICANS occurred in one patient (33.3%). Characteristics such as ECOG of 2 or higher, baseline oxygen use, and untreated CNS metastases are associated with high rates of CRS and ICANS. In 17 patients evaluable for best response in cohort 1, partial response was seen in six (35.2%) patients. No patients in cohort 2 had disease assessment performed at the time of data cutoff. Alternative CNS disease control using tarlatamab alone or with concurrent radiation provided clinical benefit to three patients.
Conclusions
Baseline risk factors such as oxygen dependence, poor ECOG performance status, bulky disease, and untreated CNS involvement may increase CRS and ICANS rates after tarlatamab. However, subsequent doses exhibited a more favorable safety profile, supporting outpatient administration and reduced observation time. CNS management strategies, including concurrent radiation or monotherapy with tarlatamab, exhibited promising efficacy. These findings highlight the need for further research into CRS and ICANS risk stratification, optimal CNS management, and efficacy in extrapulmonary small cell carcinoma through larger studies.
{"title":"Safety, Efficacy, and Central Nervous System Control in Patients with High Baseline Risk Factors Treated with Tarlatamab for SCLC or Extrapulmonary Small Cell Carcinoma","authors":"Sanjana Mullangi MD , Manidhar Reddy Lekkala MD , Sarah Blocker PharmD , Diana Kim PharmD , Jun Zhang MD , Chao Huang MD , Prakash Neupane MD , Haoran Li MD , Timothy Schieber PharmD","doi":"10.1016/j.jtocrr.2025.100875","DOIUrl":"10.1016/j.jtocrr.2025.100875","url":null,"abstract":"<div><h3>Introduction</h3><div>SCLC remains the most aggressive lung cancer with a poor prognosis. Tarlatamab, a bispecific T-cell engager, is approved for use in extensive-stage SCLC after progression on a platinum-based chemotherapy on the basis of the DeLLphi-301 trial. Because of the restrictive inclusion criteria of this trial, substantial gaps remain in our understanding of treatment for many patients.</div></div><div><h3>Methods</h3><div>We performed a retrospective chart review of patients who were treated with tarlatamab at the University of Kansas Cancer Center from May 2024 through December 2024 for SCLC (cohort 1) or extrapulmonary small cell carcinoma (EPSCC) (cohort 2). Patients were included if they received at least one dose of tarlatamab regardless of baseline characteristics.</div></div><div><h3>Results</h3><div>A total of 21 patients were included in cohort 1, and three patients were included in cohort 2. In the SCLC cohort, 14 patients (66.6%) had central nervous system (CNS) involvement, five patients (23.8%) required baseline oxygen, and five patients (23.8%) had an Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or greater. There were 13 patients (61.9%) who developed cytokine release syndrome (CRS), with grade 3 or higher CRS noted in two patients (15.3%). There were 10 patients (47.6%) who developed immune effector cell–associated neurotoxicity syndrome (ICANS), with three patients (14.2%) developing grade 3 or higher ICANS. In the three patients with extrapulmonary small cell carcinoma, any-grade CRS occurred in two patients (66.7%), and grade 1 ICANS occurred in one patient (33.3%). Characteristics such as ECOG of 2 or higher, baseline oxygen use, and untreated CNS metastases are associated with high rates of CRS and ICANS. In 17 patients evaluable for best response in cohort 1, partial response was seen in six (35.2%) patients. No patients in cohort 2 had disease assessment performed at the time of data cutoff. Alternative CNS disease control using tarlatamab alone or with concurrent radiation provided clinical benefit to three patients.</div></div><div><h3>Conclusions</h3><div>Baseline risk factors such as oxygen dependence, poor ECOG performance status, bulky disease, and untreated CNS involvement may increase CRS and ICANS rates after tarlatamab. However, subsequent doses exhibited a more favorable safety profile, supporting outpatient administration and reduced observation time. CNS management strategies, including concurrent radiation or monotherapy with tarlatamab, exhibited promising efficacy. These findings highlight the need for further research into CRS and ICANS risk stratification, optimal CNS management, and efficacy in extrapulmonary small cell carcinoma through larger studies.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 11","pages":"Article 100875"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145425162","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 : 2025-11-01DOI: 10.1016/j.jtocrr.2025.100890
Arthi Sridhar MD , Aditi Singh MD, MPH , Scott Hansen MD , Sydney Pulsipher MD , Kaushal Parikh MD , Aaron S. Mansfield MD , Anastasios Dimou MD , Julian R. Molina MD , Katherine E. Smith MD , Yolanda I. Garces MD , Sean S. Park MD , Aadel A. Chaudhuri MD, PhD , Kenneth W. Merrell MD , Kenneth R. Olivier MD , Konstantinos Leventakos MD , Dawn Owen MD, PhD , Mohamed Shanshal MD, MBBCh
Background
The eighth edition of the International Association for the Study of Lung Cancer staging project reports a 5-year overall survival (OS) for stage IIIA, B, and C NSCLC of 41%, 24%, and 12%, respectively, highlighting the need for improved treatment options. Induction chemotherapy and immune checkpoint inhibition (ID-chemo-ICI) followed by concurrent chemoradiation (cCRT) has not been adequately studied because of concerns about toxicity. We aim to describe the outcomes of patients with unresectable stage III NSCLC who received ID-chemo-ICI followed by cCRT with or without maintenance ICI.
Methods
We conducted a retrospective analysis of patients with unresectable stage III NSCLC who received ID-chemo-ICI with the intent to proceed with cCRT across all Mayo Clinic sites. Clinical end points included progression-free survival (PFS), OS, overall response rate per the Response Evaluation Criteria in Solid Tumors version 1.1, and treatment-related adverse events defined using Common Terminology Criteria for Adverse Events version 5.0.
Results
A total of 29 patients with unresectable stage III NSCLC, deemed unsuitable for upfront cCRT or surgery, with a plan to proceed with ID-chemo-ICI before cCRT, were identified. The median age was 66 years, 55% were male, most had a history of smoking (93.1%), and 100% identified as White. Tumor histologies were adenocarcinoma (69%), squamous cell carcinoma (24%), poorly differentiated NSCLC (3.4%), and sarcomatoid NSCLC (3.4%). Most were stage IIIB (44.8%), followed by IIIC (41.4%), and IIIA (13.8%). N2 and N3 disease were present in 37.9% and 55.2%, respectively. Programmed death-ligand 1 expression included less than 1% (n = 11, 38%), 1% to 49% (n = 9, 31%), greater than 50% (n = 5, 17%), and unknown (n = 4, 14%). Patients received ID-chemo-ICI with pembrolizumab (82.8%), nivolumab (13.8%), or atezolizumab (3.4%), with a median of four cycles. The overall response rate to ID-chemo-ICI was 93%. Of the cohort, 90% received cCRT, and 76% received maintenance ICI (pembrolizumab or durvalumab). The median PFS was 18 months, and the median OS was 24 months. Pneumonitis occurred in 37.9% (grade 1: 18.2%; grade 2: 63.6%; grade 3: 18%, no grade 4). Esophagitis occurred in 55.2% (grade 1–2: 93%; grade 3: 7%).
Conclusions
ID-chemo-ICI followed by cCRT seems feasible and safe for unresectable stage III NSCLC, particularly for patients unsuitable for upfront cCRT. Larger prospective trials are needed to validate these findings and optimize patient selection.
{"title":"Safety and Efficacy of Sequential Chemoimmunotherapy Followed by Concurrent Chemoradiation in Unresectable Stage III NSCLC","authors":"Arthi Sridhar MD , Aditi Singh MD, MPH , Scott Hansen MD , Sydney Pulsipher MD , Kaushal Parikh MD , Aaron S. Mansfield MD , Anastasios Dimou MD , Julian R. Molina MD , Katherine E. Smith MD , Yolanda I. Garces MD , Sean S. Park MD , Aadel A. Chaudhuri MD, PhD , Kenneth W. Merrell MD , Kenneth R. Olivier MD , Konstantinos Leventakos MD , Dawn Owen MD, PhD , Mohamed Shanshal MD, MBBCh","doi":"10.1016/j.jtocrr.2025.100890","DOIUrl":"10.1016/j.jtocrr.2025.100890","url":null,"abstract":"<div><h3>Background</h3><div>The eighth edition of the International Association for the Study of Lung Cancer staging project reports a 5-year overall survival (OS) for stage IIIA, B, and C NSCLC of 41%, 24%, and 12%, respectively, highlighting the need for improved treatment options. Induction chemotherapy and immune checkpoint inhibition (ID-chemo-ICI) followed by concurrent chemoradiation (cCRT) has not been adequately studied because of concerns about toxicity. We aim to describe the outcomes of patients with unresectable stage III NSCLC who received ID-chemo-ICI followed by cCRT with or without maintenance ICI.</div></div><div><h3>Methods</h3><div>We conducted a retrospective analysis of patients with unresectable stage III NSCLC who received ID-chemo-ICI with the intent to proceed with cCRT across all Mayo Clinic sites. Clinical end points included progression-free survival (PFS), OS, overall response rate per the Response Evaluation Criteria in Solid Tumors version 1.1, and treatment-related adverse events defined using Common Terminology Criteria for Adverse Events version 5.0.</div></div><div><h3>Results</h3><div>A total of 29 patients with unresectable stage III NSCLC, deemed unsuitable for upfront cCRT or surgery, with a plan to proceed with ID-chemo-ICI before cCRT, were identified. The median age was 66 years, 55% were male, most had a history of smoking (93.1%), and 100% identified as White. Tumor histologies were adenocarcinoma (69%), squamous cell carcinoma (24%), poorly differentiated NSCLC (3.4%), and sarcomatoid NSCLC (3.4%). Most were stage IIIB (44.8%), followed by IIIC (41.4%), and IIIA (13.8%). N2 and N3 disease were present in 37.9% and 55.2%, respectively. Programmed death-ligand 1 expression included less than 1% (n = 11, 38%), 1% to 49% (n = 9, 31%), greater than 50% (n = 5, 17%), and unknown (n = 4, 14%). Patients received ID-chemo-ICI with pembrolizumab (82.8%), nivolumab (13.8%), or atezolizumab (3.4%), with a median of four cycles. The overall response rate to ID-chemo-ICI was 93%. Of the cohort, 90% received cCRT, and 76% received maintenance ICI (pembrolizumab or durvalumab). The median PFS was 18 months, and the median OS was 24 months. Pneumonitis occurred in 37.9% (grade 1: 18.2%; grade 2: 63.6%; grade 3: 18%, no grade 4). Esophagitis occurred in 55.2% (grade 1–2: 93%; grade 3: 7%).</div></div><div><h3>Conclusions</h3><div>ID-chemo-ICI followed by cCRT seems feasible and safe for unresectable stage III NSCLC, particularly for patients unsuitable for upfront cCRT. Larger prospective trials are needed to validate these findings and optimize patient selection.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 11","pages":"Article 100890"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145474293","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 : 2025-11-01DOI: 10.1016/j.jtocrr.2025.100879
Sheng-Han Tsai MD , Jui-Hung Tsai MD , Li-Jun Chen MS , Szu-Chun Yang MD, PhD
Introduction
In the ADRIATIC trial, durvalumab consolidation therapy improved the overall survival and progression-free survival of patients with limited-stage SCLC responding to chemoradiotherapy. Based on the data, we aim to assess the cost-effectiveness of the therapy from the perspective of the Taiwanese health care sector.
Methods
Simulated patients with limited-stage SCLC responding to chemoradiotherapy were entered into a partitioned survival model comparing durvalumab consolidation with no consolidation therapy. The model inputs were derived from the ADRIATIC trial (survival outcomes, adverse events, and subsequent therapies), National Health Insurance payments (costs of physician visits, monitoring, drug administration, and end-of-life care), and the hospital cohort (utility values). A lifetime horizon and annual discount rate of 3% were applied. Subgroup, one-way deterministic, and probabilistic analyses were performed.
Results
Durvalumab consolidation therapy incurred an additional $91,734 USD and brought about 0.90 quality-adjusted life years (QALYs) gained, resulting in an incremental cost-effectiveness ratio (ICER) of $101,734 USD per QALY. The ICER remained higher than the willingness-to-pay threshold of $70,000 USD per QALY across most patient subgroups. The most influential factor for the ICER was the cost of durvalumab. If the 4-week drug cost could be reduced to $3893 USD, the ICER would fall below 70,000 USD per QALY. At the willingness-to-pay threshold, durvalumab consolidation therapy had a probability of 0.3% being cost-effective.
Conclusions
Our analysis suggests that durvalumab consolidation therapy is not cost-effective for patients with limited-stage SCLC. Reducing the price of the therapy enhances cost-effectiveness.
{"title":"Cost-Effectiveness of Durvalumab After Chemoradiotherapy in Limited-Stage SCLC","authors":"Sheng-Han Tsai MD , Jui-Hung Tsai MD , Li-Jun Chen MS , Szu-Chun Yang MD, PhD","doi":"10.1016/j.jtocrr.2025.100879","DOIUrl":"10.1016/j.jtocrr.2025.100879","url":null,"abstract":"<div><h3>Introduction</h3><div>In the ADRIATIC trial, durvalumab consolidation therapy improved the overall survival and progression-free survival of patients with limited-stage SCLC responding to chemoradiotherapy. Based on the data, we aim to assess the cost-effectiveness of the therapy from the perspective of the Taiwanese health care sector.</div></div><div><h3>Methods</h3><div>Simulated patients with limited-stage SCLC responding to chemoradiotherapy were entered into a partitioned survival model comparing durvalumab consolidation with no consolidation therapy. The model inputs were derived from the ADRIATIC trial (survival outcomes, adverse events, and subsequent therapies), National Health Insurance payments (costs of physician visits, monitoring, drug administration, and end-of-life care), and the hospital cohort (utility values). A lifetime horizon and annual discount rate of 3% were applied. Subgroup, one-way deterministic, and probabilistic analyses were performed.</div></div><div><h3>Results</h3><div>Durvalumab consolidation therapy incurred an additional $91,734 USD and brought about 0.90 quality-adjusted life years (QALYs) gained, resulting in an incremental cost-effectiveness ratio (ICER) of $101,734 USD per QALY. The ICER remained higher than the willingness-to-pay threshold of $70,000 USD per QALY across most patient subgroups. The most influential factor for the ICER was the cost of durvalumab. If the 4-week drug cost could be reduced to $3893 USD, the ICER would fall below 70,000 USD per QALY. At the willingness-to-pay threshold, durvalumab consolidation therapy had a probability of 0.3% being cost-effective.</div></div><div><h3>Conclusions</h3><div>Our analysis suggests that durvalumab consolidation therapy is not cost-effective for patients with limited-stage SCLC. Reducing the price of the therapy enhances cost-effectiveness.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 11","pages":"Article 100879"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145425160","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}
Immunotherapy has revolutionized the treatment of NSCLC. However, trials that led to approval of these agents and ongoing trials often include overly included overly restrictive exclusion criteria, limiting access for a significant proportion of patients. We propose the immunotherapy clinical trial inclusivity score (ICTIS), a scoring system to evaluate trial eligibility criteria for inclusivity.
Methods
ICTIS was developed using national guidelines and validated with a Cohen’s Kappa statistics of 0.807. Eligibility criteria for advanced NSCLC immunotherapy trials on ClinicalTrials.gov were scored using a binary scale (0 = exclusive, 1 = inclusive), with higher summed scores indicating higher inclusivity. Mean ICTIS scores were compared across lines of treatment, start date, and trial phase.
Results
The mean ICTIS score among 142 trials was 12.7 (SD 4), with 28 trials (19.7%) rated as excellent and 34 trials (23.9%) rated poor. The most restrictive criteria were Eastern Cooperative Oncology Group performance status (78.8%), organ function criteria of bilirubin (76.1%), and absolute neutrophil count (65.5%). First-line trials were significantly more exclusive to patients with pneumonitis history, with 64% exclusion versus 45.5% in second-line (χ2 = 4.917, p = 0.027). The platelet count requirement was more stringent in monotherapy trials. Inclusion of treated leptomeningeal disease improved over time (χ2 = 7.99, p = 0.018), but eligibility criteria remained consistent across different time periods, lines of treatment, and trial phases.
Conclusions
Despite the release of national guidelines, immunotherapy trials have overall retained restrictive eligibility criteria. ICTIS provides a standardized framework for evaluating inclusivity and can assist in designing immunotherapy studies to be more inclusive.
免疫疗法已经彻底改变了非小细胞肺癌的治疗。然而，导致这些药物获得批准的试验和正在进行的试验通常包括过度纳入过于严格的排除标准，限制了很大一部分患者的使用。我们提出了免疫治疗临床试验包容性评分（ICTIS），这是一个评估试验包容性资格标准的评分系统。方法sictis采用国家指南开发，采用0.807的Cohen’s Kappa统计量进行验证。临床试验网站ClinicalTrials.gov上晚期NSCLC免疫治疗试验的资格标准采用二元评分（0 =排他，1 =包容），总得分越高，包容性越高。比较不同治疗线、开始日期和试验阶段的平均ICTIS评分。结果142项试验的ICTIS平均评分为12.7 (SD 4)，其中优28项（19.7%），差34项（23.9%）。最严格的标准是东部肿瘤合作组表现状态（78.8%）、胆红素器官功能标准（76.1%）和绝对中性粒细胞计数（65.5%）。一线试验对有肺炎史的患者的排他性更高，排他性为64%，二线试验为45.5% （χ2 = 4.917, p = 0.027）。单药治疗试验对血小板计数的要求更为严格。随着时间的推移，治疗后的轻脑膜疾病的纳入情况有所改善（χ2 = 7.99, p = 0.018），但不同时间段、治疗线和试验阶段的入选标准保持一致。尽管发布了国家指南，但免疫治疗试验总体上保留了限制性的资格标准。ICTIS提供了一个评估包容性的标准化框架，可以帮助设计更具包容性的免疫治疗研究。
{"title":"ICTIS: A Novel Scoring System to Assess the Inclusivity of Advanced NSCLC Immunotherapy Trials","authors":"Kira Nguyen , Ashley Wei , Srinivas Govindan MD , Eziafa Oduah MD, PhD , Nagashree Seetharamu MD , Wint Yan Aung MD","doi":"10.1016/j.jtocrr.2025.100878","DOIUrl":"10.1016/j.jtocrr.2025.100878","url":null,"abstract":"<div><h3>Introduction</h3><div>Immunotherapy has revolutionized the treatment of NSCLC. However, trials that led to approval of these agents and ongoing trials often include overly included overly restrictive exclusion criteria, limiting access for a significant proportion of patients. We propose the immunotherapy clinical trial inclusivity score (ICTIS), a scoring system to evaluate trial eligibility criteria for inclusivity.</div></div><div><h3>Methods</h3><div>ICTIS was developed using national guidelines and validated with a Cohen’s Kappa statistics of 0.807. Eligibility criteria for advanced NSCLC immunotherapy trials on <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> were scored using a binary scale (0 = exclusive, 1 = inclusive), with higher summed scores indicating higher inclusivity. Mean ICTIS scores were compared across lines of treatment, start date, and trial phase.</div></div><div><h3>Results</h3><div>The mean ICTIS score among 142 trials was 12.7 (SD 4), with 28 trials (19.7%) rated as excellent and 34 trials (23.9%) rated poor. The most restrictive criteria were Eastern Cooperative Oncology Group performance status (78.8%), organ function criteria of bilirubin (76.1%), and absolute neutrophil count (65.5%). First-line trials were significantly more exclusive to patients with pneumonitis history, with 64% exclusion versus 45.5% in second-line (χ<sup>2</sup> = 4.917, <em>p</em> = 0.027). The platelet count requirement was more stringent in monotherapy trials. Inclusion of treated leptomeningeal disease improved over time (χ<sup>2</sup> = 7.99, <em>p</em> = 0.018), but eligibility criteria remained consistent across different time periods, lines of treatment, and trial phases.</div></div><div><h3>Conclusions</h3><div>Despite the release of national guidelines, immunotherapy trials have overall retained restrictive eligibility criteria. ICTIS provides a standardized framework for evaluating inclusivity and can assist in designing immunotherapy studies to be more inclusive.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 11","pages":"Article 100878"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145425195","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 : 2025-10-30DOI: 10.1016/j.jtocrr.2025.100929
Niels Reinmuth MD , Sébastien Couraud MD, PhD , Luis Paz-Ares MD, PhD , Marina Chiara Garassino MD , Shobhit Baijal MBBS, BSc , Davey Daniel MD , Pilar Garrido MD, PhD , Terufumi Kato MD , Ivor Percent MD , Achim Rittmeyer MD , Hector Soto Parra MD , Sabeen Mekan MD , Mira Patel PhD , Matthew Radford PhD , Eric Zhang PhD , Christopher G. Pelligra MS , Shien Guo PhD , Enriqueta Felip MD, PhD
Introduction
In the phase 3 EVOKE-01 trial (NCT05089734), sacituzumab govitecan (SG) exhibited a numerical improvement in overall survival and tolerability compared with docetaxel in patients with metastatic NSCLC previously treated with platinum-based chemotherapy and programmed cell death protein (ligand) 1 inhibitors, although results were not statistically significant. This analysis evaluated health-related quality of life (HRQoL) data from EVOKE-01.
Methods
Patients (N = 603) were randomized 1:1 to SG (n = 299) or docetaxel (n = 304) in 21-day cycles. HRQoL was assessed by the NSCLC Symptom Assessment Questionnaire (NSCLC-SAQ), European Organization for Research and Treatment of Cancer Quality of Life questionnaire–Core 30 (QLQ-C30), and EuroQol 5 Dimension 3-level questionnaire. Least square mean changes from baseline at week 25, time to first meaningful deterioration or death, and time to confirmed deterioration were analyzed.
Results
SG exhibited significantly and meaningfully better effects than docetaxel on NSCLC-SAQ shortness of breath (SoB), fatigue, total score, and on QLQ-C30 role functioning, fatigue, and dyspnea. Time to first meaningful deterioration or death favored SG over docetaxel for NSCLC-SAQ SoB (hazard ratio [95% confidence interval ]: 0.75 [0.61–0.91]), fatigue (0.70 [0.57–0.86]), and total score (0.80 [0.66–0.97]); QLQ-C30 fatigue (0.80 [0.66–0.96]) and dyspnea (0.74 [0.60–0.90]); and EuroQol visual analog scale (0.79 [0.65–0.96]). The time to confirmed deterioration favored SG over docetaxel for NSCLC-SAQ SoB (0.59 [0.44–0.77]) and fatigue (0.70 [0.52–0.95]), and QLQ-C30 fatigue (0.75 [0.59–0.95]).
Conclusions
These exploratory results suggest that SG may benefit HRQoL over docetaxel, supporting SG as an active therapeutic agent for metastatic NSCLC post platinum-based and programmed cell death protein (ligand) 1 inhibitor therapy.
{"title":"Patient-Reported Symptoms and Quality of Life With Sacituzumab Govitecan Versus Docetaxel in Metastatic NSCLC: The Phase 3, Randomized EVOKE-01 Trial","authors":"Niels Reinmuth MD , Sébastien Couraud MD, PhD , Luis Paz-Ares MD, PhD , Marina Chiara Garassino MD , Shobhit Baijal MBBS, BSc , Davey Daniel MD , Pilar Garrido MD, PhD , Terufumi Kato MD , Ivor Percent MD , Achim Rittmeyer MD , Hector Soto Parra MD , Sabeen Mekan MD , Mira Patel PhD , Matthew Radford PhD , Eric Zhang PhD , Christopher G. Pelligra MS , Shien Guo PhD , Enriqueta Felip MD, PhD","doi":"10.1016/j.jtocrr.2025.100929","DOIUrl":"10.1016/j.jtocrr.2025.100929","url":null,"abstract":"<div><h3>Introduction</h3><div>In the phase 3 EVOKE-01 trial (NCT05089734), sacituzumab govitecan (SG) exhibited a numerical improvement in overall survival and tolerability compared with docetaxel in patients with metastatic NSCLC previously treated with platinum-based chemotherapy and programmed cell death protein (ligand) 1 inhibitors, although results were not statistically significant. This analysis evaluated health-related quality of life (HRQoL) data from EVOKE-01.</div></div><div><h3>Methods</h3><div>Patients (N = 603) were randomized 1:1 to SG (n = 299) or docetaxel (n = 304) in 21-day cycles. HRQoL was assessed by the NSCLC Symptom Assessment Questionnaire (NSCLC-SAQ), European Organization for Research and Treatment of Cancer Quality of Life questionnaire–Core 30 (QLQ-C30), and EuroQol 5 Dimension 3-level questionnaire. Least square mean changes from baseline at week 25, time to first meaningful deterioration or death, and time to confirmed deterioration were analyzed.</div></div><div><h3>Results</h3><div>SG exhibited significantly and meaningfully better effects than docetaxel on NSCLC-SAQ shortness of breath (SoB), fatigue, total score, and on QLQ-C30 role functioning, fatigue, and dyspnea. Time to first meaningful deterioration or death favored SG over docetaxel for NSCLC-SAQ SoB (hazard ratio [95% confidence interval ]: 0.75 [0.61–0.91]), fatigue (0.70 [0.57–0.86]), and total score (0.80 [0.66–0.97]); QLQ-C30 fatigue (0.80 [0.66–0.96]) and dyspnea (0.74 [0.60–0.90]); and EuroQol visual analog scale (0.79 [0.65–0.96]). The time to confirmed deterioration favored SG over docetaxel for NSCLC-SAQ SoB (0.59 [0.44–0.77]) and fatigue (0.70 [0.52–0.95]), and QLQ-C30 fatigue (0.75 [0.59–0.95]).</div></div><div><h3>Conclusions</h3><div>These exploratory results suggest that SG may benefit HRQoL over docetaxel, supporting SG as an active therapeutic agent for metastatic NSCLC post platinum-based and programmed cell death protein (ligand) 1 inhibitor therapy.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 2","pages":"Article 100929"},"PeriodicalIF":3.5,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980962","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}
Preoperative immune-related adverse events (irAEs) during neoadjuvant chemoimmunotherapy for resectable non-small cell lung cancer (NSCLC) remain poorly characterized. We aimed to evaluate their frequency, clinical impact, and associated risk factors.
Methods
This prespecified subanalysis of the multicenter CReGYT-04 Neo-Venus study retrospectively examined 130 patients with resectable NSCLC (stage IIA-IIIB, Union for International Cancer Control, eighth edition) treated with neoadjuvant nivolumab plus platinum-doublet chemotherapy. Clinical data were collected from 29 Japanese institutions. Patients were stratified according to the presence or absence of preoperative irAEs. Exploratory logistic regression was used to identify predictive factors.
Results
Preoperative irAEs were observed in 18.5% of the patients (n = 24). Patients with irAEs had a significantly lower neoadjuvant therapy completion rate (58.3% versus 92.5%, p <0.001) and a higher incidence of cancelled surgery (21.7% versus 5.8%, p = 0.029) than those without irAEs. There were 18 patients (78.3%) with irAEs who underwent surgical resection. R0 resection was achieved in 94.4%. The postoperative complication rates and length of hospital stay were comparable between the groups. The major pathologic response rate (38.9% versus 63.1%) and pathologic complete response rate (27.8% versus 36.8%) were lower in patients with preoperative irAEs. Tumor size greater than 3.8 cm and eosinophil fraction greater than or equal to 2.0% were identified as exploratory predictors of preoperative irAEs.
Conclusion
Preoperative irAEs occurred in approximately 20% of patients with resectable NSCLC treated with neoadjuvant nivolumab plus chemotherapy and were associated with treatment discontinuation and cancellation of surgery. Nevertheless, curative-intent surgery remained feasible and achieved acceptable perioperative outcomes in most patients with preoperative irAEs.
在可切除的非小细胞肺癌（NSCLC）的新辅助化疗免疫治疗期间，术前免疫相关不良事件（irAEs）的特征仍然很差。我们的目的是评估其发生频率、临床影响和相关危险因素。方法：这项预先指定的多中心CReGYT-04 Neo-Venus研究回顾性分析了130例接受新辅助纳武单抗加铂双药化疗的可切除非小细胞肺癌（iiia - iiib期，国际癌症控制联盟，第八版）患者。临床数据收集自日本29家机构。根据术前是否有irae对患者进行分层。采用探索性逻辑回归确定预测因素。结果24例患者（18.5%）术后出现irae。irAEs患者的新辅助治疗完成率（58.3% vs . 92.5%, p <0.001）明显低于无irAEs患者，而取消手术的发生率（21.7% vs . 5.8%, p = 0.029）高于无irAEs患者。有18例（78.3%）的irae患者接受了手术切除。R0切除率为94.4%。术后并发症发生率和住院时间在两组间具有可比性。术前irae患者的主要病理缓解率（38.9%对63.1%）和病理完全缓解率（27.8%对36.8%）较低。肿瘤大小大于3.8 cm和嗜酸性粒细胞分数大于或等于2.0%被确定为术前irae的探索性预测因子。结论在接受新辅助纳武单抗加化疗的可切除NSCLC患者中，约20%的患者发生了术前irae，并且与治疗停止和手术取消有关。尽管如此，以治愈为目的的手术仍然是可行的，并且在大多数术前irae患者中获得了可接受的围手术期结果。
{"title":"Preoperative Immune-Related Adverse Events in Resectable NSCLC Treated With Neoadjuvant Nivolumab Plus Chemotherapy: A Multicenter Retrospective Analysis","authors":"Takuya Watanabe MD , Kotaro Nomura MD , Shinkichi Takamori MD , Shinya Tane MD , Shuta Ohara MD , Hana Oiki MD , Shinya Katsumata MD , Makoto Endo MD , Satoshi Takamori MD , Marina Nakatsuka MD , Hironori Tenpaku MD , Ryuji Nakamura MD , Hirotsugu Notsuda MD , Kei Namba MD , Kentaro Minegishi MD , Masayuki Tanahashi MD , Masahiro Tsuboi MD , Junichi Soh MD , Mototsugu Shimokawa MD , Yasuhisa Ohde MD","doi":"10.1016/j.jtocrr.2025.100930","DOIUrl":"10.1016/j.jtocrr.2025.100930","url":null,"abstract":"<div><h3>Introduction</h3><div>Preoperative immune-related adverse events (irAEs) during neoadjuvant chemoimmunotherapy for resectable non-small cell lung cancer (NSCLC) remain poorly characterized. We aimed to evaluate their frequency, clinical impact, and associated risk factors.</div></div><div><h3>Methods</h3><div>This prespecified subanalysis of the multicenter CReGYT-04 Neo-Venus study retrospectively examined 130 patients with resectable NSCLC (stage IIA-IIIB, Union for International Cancer Control, eighth edition) treated with neoadjuvant nivolumab plus platinum-doublet chemotherapy. Clinical data were collected from 29 Japanese institutions. Patients were stratified according to the presence or absence of preoperative irAEs. Exploratory logistic regression was used to identify predictive factors.</div></div><div><h3>Results</h3><div>Preoperative irAEs were observed in 18.5% of the patients (n = 24). Patients with irAEs had a significantly lower neoadjuvant therapy completion rate (58.3% versus 92.5%, <em>p</em> <0.001) and a higher incidence of cancelled surgery (21.7% versus 5.8%, <em>p</em> = 0.029) than those without irAEs. There were 18 patients (78.3%) with irAEs who underwent surgical resection. R0 resection was achieved in 94.4%. The postoperative complication rates and length of hospital stay were comparable between the groups. The major pathologic response rate (38.9% versus 63.1%) and pathologic complete response rate (27.8% versus 36.8%) were lower in patients with preoperative irAEs. Tumor size greater than 3.8 cm and eosinophil fraction greater than or equal to 2.0% were identified as exploratory predictors of preoperative irAEs.</div></div><div><h3>Conclusion</h3><div>Preoperative irAEs occurred in approximately 20% of patients with resectable NSCLC treated with neoadjuvant nivolumab plus chemotherapy and were associated with treatment discontinuation and cancellation of surgery. Nevertheless, curative-intent surgery remained feasible and achieved acceptable perioperative outcomes in most patients with preoperative irAEs.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 1","pages":"Article 100930"},"PeriodicalIF":3.5,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798011","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 : 2025-10-30DOI: 10.1016/j.jtocrr.2025.100927
Van-Anh Nguyen Hoang MSc , Ngoc Nguyen BSc , Tu Nguyen MSc , Duy Sinh Nguyen MD, PhD , Hoai-Nghia Nguyen PhD , Lan N. Tu PhD
Background
Circulating tumor DNA (ctDNA) is a promising prognostic biomarker in early-stage NSCLC. The typical tumor-informed method of ctDNA testing requires tissue specimens of high quality, which is a challenge in developing countries. Tumor-naive approach is an alternative, but the performance of the two methods has not been directly compared using the same samples and platform.
Methods
We retrospectively analyzed tumor and blood samples of patients with early-stage NSCLC enrolled in our published study. For analytical performance, pretreatment samples of 42 patients and 50 healthy donors were used to assess the accuracy of ctDNA detection. For clinical performance, 176 postsurgical blood samples of 76 patients with NSCLC were analyzed to compare the ctDNA status with recorded clinical recurrence. The tumor-informed method evaluated personalized mutations and a fixed 500-hotspot panel, whereas the tumor-naive method combined predesigned mutation panels and nonmutation genome-wide features of ctDNA.
Results
The tumor-informed assay had 66.7% sensitivity and 99.3% specificity for detecting ctDNA in early-stage NSCLC, higher than the tumor-naive assay with 52.6% sensitivity and 95.7% specificity. Postsurgical ctDNA status determined by both methods had significant prognostic value to predict recurrence ahead of clinical diagnosis (hazard ratio >100, p < 0.0001). Tumor-informed ctDNA achieved 86.7% sensitivity to detect recurrence, and the 500-hotspot panel improved the ctDNA detection rate for cases with suboptimal tissue specimens. Tumor-naive ctDNA had 80.0% sensitivity to detect recurrence, and integration of nonmutation features was crucial.
Conclusions
Both methods exhibited high accuracy in detecting residual cancer in NSCLC. The tumor-naive approach is a reliable alternative when high-quality tissue specimens are unavailable.
循环肿瘤DNA （ctDNA）是早期非小细胞肺癌预后的一种有前景的生物标志物。典型的肿瘤知情ctDNA检测方法需要高质量的组织标本，这在发展中国家是一个挑战。肿瘤初始方法是一种替代方法，但使用相同的样本和平台，两种方法的性能尚未直接进行比较。方法回顾性分析纳入本研究的早期非小细胞肺癌患者的肿瘤和血液样本。为了分析性能，使用42名患者和50名健康供体的预处理样本来评估ctDNA检测的准确性。在临床表现方面，我们分析了76例NSCLC患者的176份术后血液样本，将ctDNA状态与临床复发记录进行比较。肿瘤知情方法评估个性化突变和固定的500个热点面板，而肿瘤初始方法结合了预先设计的突变面板和ctDNA的非突变全基因组特征。结果肿瘤知情法检测早期NSCLC ctDNA的灵敏度为66.7%，特异性为99.3%，高于肿瘤未知情法检测ctDNA的灵敏度为52.6%，特异性为95.7%。两种方法检测的术后ctDNA状态对临床诊断前预测复发具有显著的预后价值（风险比>；100, p < 0.0001）。肿瘤知情ctDNA检测复发的敏感性达到86.7%，500热点面板提高了组织标本次优病例的ctDNA检出率。肿瘤初始ctDNA检测复发的敏感性为80.0%，非突变特征的整合至关重要。结论两种方法对非小细胞肺癌残留癌的检测准确率较高。当无法获得高质量的组织标本时，肿瘤原位方法是一种可靠的替代方法。
{"title":"Direct Comparison of Tumor-Informed and Tumor-Naive Circulating Tumor DNA Assays for Recurrence Detection in Early-Stage NSCLC","authors":"Van-Anh Nguyen Hoang MSc , Ngoc Nguyen BSc , Tu Nguyen MSc , Duy Sinh Nguyen MD, PhD , Hoai-Nghia Nguyen PhD , Lan N. Tu PhD","doi":"10.1016/j.jtocrr.2025.100927","DOIUrl":"10.1016/j.jtocrr.2025.100927","url":null,"abstract":"<div><h3>Background</h3><div>Circulating tumor DNA (ctDNA) is a promising prognostic biomarker in early-stage NSCLC. The typical tumor-informed method of ctDNA testing requires tissue specimens of high quality, which is a challenge in developing countries. Tumor-naive approach is an alternative, but the performance of the two methods has not been directly compared using the same samples and platform.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed tumor and blood samples of patients with early-stage NSCLC enrolled in our published study. For analytical performance, pretreatment samples of 42 patients and 50 healthy donors were used to assess the accuracy of ctDNA detection. For clinical performance, 176 postsurgical blood samples of 76 patients with NSCLC were analyzed to compare the ctDNA status with recorded clinical recurrence. The tumor-informed method evaluated personalized mutations and a fixed 500-hotspot panel, whereas the tumor-naive method combined predesigned mutation panels and nonmutation genome-wide features of ctDNA.</div></div><div><h3>Results</h3><div>The tumor-informed assay had 66.7% sensitivity and 99.3% specificity for detecting ctDNA in early-stage NSCLC, higher than the tumor-naive assay with 52.6% sensitivity and 95.7% specificity. Postsurgical ctDNA status determined by both methods had significant prognostic value to predict recurrence ahead of clinical diagnosis (hazard ratio >100, <em>p</em> < 0.0001). Tumor-informed ctDNA achieved 86.7% sensitivity to detect recurrence, and the 500-hotspot panel improved the ctDNA detection rate for cases with suboptimal tissue specimens. Tumor-naive ctDNA had 80.0% sensitivity to detect recurrence, and integration of nonmutation features was crucial.</div></div><div><h3>Conclusions</h3><div>Both methods exhibited high accuracy in detecting residual cancer in NSCLC. The tumor-naive approach is a reliable alternative when high-quality tissue specimens are unavailable.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 1","pages":"Article 100927"},"PeriodicalIF":3.5,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798010","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 : 2025-10-29DOI: 10.1016/j.jtocrr.2025.100928
Adele Bonato MD , Claudia Parisi MD , Priscilla Cascetta MD , Anna Reni MD , May-Lucie Meyer MD , Mariona Riudavets MD, PhD , David Planchard MD, PhD , Benjamin Besse MD, PhD , Jordi Remon MD , Francesco Facchinetti MD, PhD , Lorenzo Belluomini MD, PhD , Lisa Derosa MD, PhD , Fabrice Barlesi MD, PhD
Background
Although most phase III pivotal trials have set the duration of immune checkpoint blockers (ICB) for advanced NSCLC at 2 years, the criteria for safely discontinuing ICB remain undefined. Growing evidence links ICB efficacy to gut microbiota, positioning gut microbial taxonomic profiling as a promising biomarker to guide treatment decisions. We performed a retrospective analysis exploring clinical outcomes and the utility of multiomic decision-making tools in patients with NSCLC at Gustave Roussy who completed 24 months of ICB-based therapy without disease progression (PD).
Methods
Patients receiving ICB between July 2016 and January 2023 were identified from the ONCOBIOTICS (NCT04567446) and STING (NCT04932525) study datasets. We selected those who reached 24 months of treatment without disease progression. Clinical characteristics and multiomic assessments, including gut microbiota profiling (TOPOSCORE by whole-genome sequencing), positron emission tomography–18-fluorodeoxyglucose imaging, and circulating tumor DNA, collected at 24 months, were analyzed. Key outcomes included overall survival (OS), progression-free survival (PFS), and PFS rates at 24 months after the completion of 2 years of ICB, stratified by molecular, metabolic, and microbial signatures.
Results
Out of 123 patients treated for at least 18 months, 35 completed 24 months, with 31 eligible for the analysis. Of these, 68% continued ICB, whereas 32% discontinued therapy at the physician’s decision. Clinical characteristics were similar across groups. After a median follow-up of 59.1 months, OS and PFS did not differ significantly between those who discontinued and those who continued treatment (OS p = 0.9012). Among all multiomic tools, gut microbiota composition exhibited a trend (though not statistically significant) association with PFS rates at 24 months after the completion of 2 years of ICB. Patients with a favorable microbiota profile had a higher rate of sustained response at 24 months compared with those with dysbiotic signatures (81% versus 44%, respectively, p = 0.0870).
Conclusions
Discontinuing ICB after 24 months did not negatively impact OS in our real-world cohort. Although limited by the small sample size, these findings support the potential of gut microbiota profiling as a promising tool to guide ICB duration. Integrating a translational multiomic algorithm, in particular microbial signals, may help personalize treatment strategies and safely shorten immunotherapy courses.
尽管大多数III期关键试验已将晚期NSCLC的免疫检查点阻断剂（ICB）的持续时间设定为2年，但安全停用ICB的标准仍未明确。越来越多的证据表明ICB疗效与肠道微生物群有关，将肠道微生物分类分析定位为指导治疗决策的有前途的生物标志物。我们进行了一项回顾性分析，探讨了Gustave Roussy非小细胞肺癌患者的临床结果和多组决策工具的实用性，这些患者完成了24个月的基于icb的无疾病进展（PD）治疗。方法从ONCOBIOTICS （NCT04567446）和STING （NCT04932525）研究数据集中筛选出2016年7月至2023年1月接受ICB治疗的患者。我们选择了那些治疗24个月无疾病进展的患者。临床特征和多组学评估，包括肠道微生物群分析（全基因组测序TOPOSCORE），正电子发射断层扫描- 18-氟脱氧葡萄糖成像，以及24个月时收集的循环肿瘤DNA进行分析。主要结局包括总生存期（OS）、无进展生存期（PFS）和完成2年ICB后24个月的PFS率，并根据分子、代谢和微生物特征进行分层。结果123例患者治疗至少18个月，35例完成24个月，其中31例符合分析条件。其中，68%的患者继续进行ICB治疗，而32%的患者在医生的决定下停止治疗。各组临床特征相似。中位随访59.1个月后，停止治疗组和继续治疗组的OS和PFS无显著差异（OS p = 0.9012）。在所有多组学工具中，在完成2年ICB后的24个月，肠道微生物群组成与PFS率显示出趋势（尽管没有统计学意义）。具有良好微生物群特征的患者在24个月时的持续缓解率高于具有不良微生物群特征的患者（分别为81%对44%，p = 0.0870）。结论：在我们的真实队列中，24个月后停用ICB对OS没有负面影响。尽管受样本量小的限制，这些发现支持肠道微生物群分析作为指导ICB持续时间的有前途的工具的潜力。整合翻译多组算法，特别是微生物信号，可能有助于个性化治疗策略和安全地缩短免疫治疗疗程。
{"title":"Gut Dysbiosis as a Potential Guide for Immunotherapy (Dis)Continuation After 2 Years in NSCLC: A Brief Report","authors":"Adele Bonato MD , Claudia Parisi MD , Priscilla Cascetta MD , Anna Reni MD , May-Lucie Meyer MD , Mariona Riudavets MD, PhD , David Planchard MD, PhD , Benjamin Besse MD, PhD , Jordi Remon MD , Francesco Facchinetti MD, PhD , Lorenzo Belluomini MD, PhD , Lisa Derosa MD, PhD , Fabrice Barlesi MD, PhD","doi":"10.1016/j.jtocrr.2025.100928","DOIUrl":"10.1016/j.jtocrr.2025.100928","url":null,"abstract":"<div><h3>Background</h3><div>Although most phase III pivotal trials have set the duration of immune checkpoint blockers (ICB) for advanced NSCLC at 2 years, the criteria for safely discontinuing ICB remain undefined. Growing evidence links ICB efficacy to gut microbiota, positioning gut microbial taxonomic profiling as a promising biomarker to guide treatment decisions. We performed a retrospective analysis exploring clinical outcomes and the utility of multiomic decision-making tools in patients with NSCLC at Gustave Roussy who completed 24 months of ICB-based therapy without disease progression (PD).</div></div><div><h3>Methods</h3><div>Patients receiving ICB between July 2016 and January 2023 were identified from the ONCOBIOTICS (NCT04567446) and STING (NCT04932525) study datasets. We selected those who reached 24 months of treatment without disease progression. Clinical characteristics and multiomic assessments, including gut microbiota profiling (TOPOSCORE by whole-genome sequencing), positron emission tomography–18-fluorodeoxyglucose imaging, and circulating tumor DNA, collected at 24 months, were analyzed. Key outcomes included overall survival (OS), progression-free survival (PFS), and PFS rates at 24 months after the completion of 2 years of ICB, stratified by molecular, metabolic, and microbial signatures.</div></div><div><h3>Results</h3><div>Out of 123 patients treated for at least 18 months, 35 completed 24 months, with 31 eligible for the analysis. Of these, 68% continued ICB, whereas 32% discontinued therapy at the physician’s decision. Clinical characteristics were similar across groups. After a median follow-up of 59.1 months, OS and PFS did not differ significantly between those who discontinued and those who continued treatment (OS <em>p</em> = 0.9012). Among all multiomic tools, gut microbiota composition exhibited a trend (though not statistically significant) association with PFS rates at 24 months after the completion of 2 years of ICB. Patients with a favorable microbiota profile had a higher rate of sustained response at 24 months compared with those with dysbiotic signatures (81% versus 44%, respectively, <em>p</em> = 0.0870).</div></div><div><h3>Conclusions</h3><div>Discontinuing ICB after 24 months did not negatively impact OS in our real-world cohort. Although limited by the small sample size, these findings support the potential of gut microbiota profiling as a promising tool to guide ICB duration. Integrating a translational multiomic algorithm, in particular microbial signals, may help personalize treatment strategies and safely shorten immunotherapy courses.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 1","pages":"Article 100928"},"PeriodicalIF":3.5,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798012","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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