JTO Clinical and Research Reports最新文献

{"title":"Thymic Neuroendocrine Tumors: Evolving Insights and Innovative Approaches","authors":"Erica Pietroluongo MD, PhD ,&nbsp;Christine M. Bestvina MD ,&nbsp;Rachel Brattin ,&nbsp;Pietro De Placido MD, PhD ,&nbsp;Anna Di Lello MD ,&nbsp;Waqas Haque MD, MPH ,&nbsp;Alessandra Esposito PhD ,&nbsp;Roberto Bianco MD, PhD ,&nbsp;Noura Choudhury MD ,&nbsp;Marina Chiara Garassino MD","doi":"10.1016/j.jtocrr.2025.100935","DOIUrl":"10.1016/j.jtocrr.2025.100935","url":null,"abstract":"<div><h3>Introduction</h3><div>Thymic neuroendocrine tumors (TNENs) are exceptionally rare and a clinically heterogeneous malignancy, often diagnosed at an advanced stage and lacking standardized treatment algorithms. Due to the scarcity of dedicated evidence, most therapeutic strategies are extrapolated from other neuroendocrine neoplasms.</div></div><div><h3>Methods</h3><div>This narrative review provides an updated overview of current and emerging treatment approaches for TNENs, focusing on histology-driven strategies and the evolving role of targeted and radionuclide therapies. A comprehensive literature search was conducted through PubMed/MEDLINE and Embase from January 1, 2000, up to May 31, 2025, integrating retrospective series, real-world data, and ongoing clinical trials.</div></div><div><h3>Results</h3><div>Surgical resection remains the cornerstone of treatment whenever feasible. The benefit of adjuvant therapy in well-differentiated tumors is unclear, whereas thymic neuroendocrine carcinomas often require multimodal approaches, including platinum–etoposide chemotherapy and radiotherapy. Retrospective evidence suggests that even well-differentiated, high-grade tumors may respond to cytotoxic agents. Somatostatin analogues are widely used in indolent or peptide receptor-positive tumors, whereas everolimus and, more recently, cabozantinib represent options for progressive disease. Peptide receptor radionuclide therapy has demonstrated encouraging results in somatostatin receptor–positive tumors and is currently under further investigation in prospective trials involving thymic primaries. However, the 5-year overall survival rate varies significantly (approximately 28%–80%), underlining an urgent need for prospective, subtype-specific studies.</div></div><div><h3>Conclusions</h3><div>The management of TNENs requires a multidisciplinary and individualized approach based on histologic subtype, somatostatin receptor status, and disease aggressiveness. Despite promising therapeutic options, robust prospective data remain limited. The integration of TNENs into basket trials, the molecular refinement of prognostic subgroups (e.g., NET G3), and the conduct of dedicated multicenter prospective studies are urgently needed to define optimal treatment algorithms and improve clinical outcomes in these rare entities.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 2","pages":"Article 100935"},"PeriodicalIF":3.5,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980963","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}

{"title":"Characteristics of Short-Term Survivors With ALK or ROS1-Altered Metastatic NSCLC","authors":"Kai-Lin Liu BA, BS ,&nbsp;Alex Watts MS ,&nbsp;Connor B. Grady MPH ,&nbsp;Geoffrey Liu MD, MSc ,&nbsp;Devalben Patel BSc, MLT ,&nbsp;Karmugi Balaratnam MD ,&nbsp;Stephen V. Liu MD ,&nbsp;Gabriela Bravo Montenegro MD ,&nbsp;Yunan Nie MD ,&nbsp;Jorge Nieva MD ,&nbsp;Amanda Herrmann MD ,&nbsp;Kristen Marrone MD ,&nbsp;Vincent Lam MD ,&nbsp;Fangdi Sun MD ,&nbsp;Jonathan Dowell MD ,&nbsp;William Schwartzman MD ,&nbsp;Vamsidhar Velcheti MD ,&nbsp;Olivia Fankuchen MD, MS ,&nbsp;Tasfiq Ullah MD ,&nbsp;Liza Villaruz MD ,&nbsp;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 &lt;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, &lt;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, &lt; 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}

{"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 ,&nbsp;Qingsong Pang MD ,&nbsp;Rong Yu MD ,&nbsp;Zhengfei Zhu MD ,&nbsp;Jiangqiong Huang MD ,&nbsp;Yufeng Cheng MD ,&nbsp;Diansheng Zhong MD ,&nbsp;Hongbo Wu MD ,&nbsp;Seung Soo Yoo PhD ,&nbsp;Tracy Dobbs MD ,&nbsp;Zinan Bao MD ,&nbsp;Yunxia Zuo MD ,&nbsp;Yujuan Gao PhD ,&nbsp;Pu Sun PhD ,&nbsp;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}

{"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 ,&nbsp;Manidhar Reddy Lekkala MD ,&nbsp;Sarah Blocker PharmD ,&nbsp;Diana Kim PharmD ,&nbsp;Jun Zhang MD ,&nbsp;Chao Huang MD ,&nbsp;Prakash Neupane MD ,&nbsp;Haoran Li MD ,&nbsp;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}

{"title":"Safety and Efficacy of Sequential Chemoimmunotherapy Followed by Concurrent Chemoradiation in Unresectable Stage III NSCLC","authors":"Arthi Sridhar MD ,&nbsp;Aditi Singh MD, MPH ,&nbsp;Scott Hansen MD ,&nbsp;Sydney Pulsipher MD ,&nbsp;Kaushal Parikh MD ,&nbsp;Aaron S. Mansfield MD ,&nbsp;Anastasios Dimou MD ,&nbsp;Julian R. Molina MD ,&nbsp;Katherine E. Smith MD ,&nbsp;Yolanda I. Garces MD ,&nbsp;Sean S. Park MD ,&nbsp;Aadel A. Chaudhuri MD, PhD ,&nbsp;Kenneth W. Merrell MD ,&nbsp;Kenneth R. Olivier MD ,&nbsp;Konstantinos Leventakos MD ,&nbsp;Dawn Owen MD, PhD ,&nbsp;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}

{"title":"Cost-Effectiveness of Durvalumab After Chemoradiotherapy in Limited-Stage SCLC","authors":"Sheng-Han Tsai MD ,&nbsp;Jui-Hung Tsai MD ,&nbsp;Li-Jun Chen MS ,&nbsp;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}

{"title":"ICTIS: A Novel Scoring System to Assess the Inclusivity of Advanced NSCLC Immunotherapy Trials","authors":"Kira Nguyen ,&nbsp;Ashley Wei ,&nbsp;Srinivas Govindan MD ,&nbsp;Eziafa Oduah MD, PhD ,&nbsp;Nagashree Seetharamu MD ,&nbsp;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 (χ² = 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 (χ² = 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}

{"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 ,&nbsp;Sébastien Couraud MD, PhD ,&nbsp;Luis Paz-Ares MD, PhD ,&nbsp;Marina Chiara Garassino MD ,&nbsp;Shobhit Baijal MBBS, BSc ,&nbsp;Davey Daniel MD ,&nbsp;Pilar Garrido MD, PhD ,&nbsp;Terufumi Kato MD ,&nbsp;Ivor Percent MD ,&nbsp;Achim Rittmeyer MD ,&nbsp;Hector Soto Parra MD ,&nbsp;Sabeen Mekan MD ,&nbsp;Mira Patel PhD ,&nbsp;Matthew Radford PhD ,&nbsp;Eric Zhang PhD ,&nbsp;Christopher G. Pelligra MS ,&nbsp;Shien Guo PhD ,&nbsp;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}

{"title":"Preoperative Immune-Related Adverse Events in Resectable NSCLC Treated With Neoadjuvant Nivolumab Plus Chemotherapy: A Multicenter Retrospective Analysis","authors":"Takuya Watanabe MD ,&nbsp;Kotaro Nomura MD ,&nbsp;Shinkichi Takamori MD ,&nbsp;Shinya Tane MD ,&nbsp;Shuta Ohara MD ,&nbsp;Hana Oiki MD ,&nbsp;Shinya Katsumata MD ,&nbsp;Makoto Endo MD ,&nbsp;Satoshi Takamori MD ,&nbsp;Marina Nakatsuka MD ,&nbsp;Hironori Tenpaku MD ,&nbsp;Ryuji Nakamura MD ,&nbsp;Hirotsugu Notsuda MD ,&nbsp;Kei Namba MD ,&nbsp;Kentaro Minegishi MD ,&nbsp;Masayuki Tanahashi MD ,&nbsp;Masahiro Tsuboi MD ,&nbsp;Junichi Soh MD ,&nbsp;Mototsugu Shimokawa MD ,&nbsp;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> &lt;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}

{"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 ,&nbsp;Ngoc Nguyen BSc ,&nbsp;Tu Nguyen MSc ,&nbsp;Duy Sinh Nguyen MD, PhD ,&nbsp;Hoai-Nghia Nguyen PhD ,&nbsp;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 &gt;100, <em>p</em> &lt; 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}