JTO Clinical and Research Reports最新文献

{"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":"Monotherapy With Immune Checkpoint Blockade Improves Survival Outcomes in KRAS-Mutant but Not KRAS Wild-Type Metastatic Lung Adenocarcinoma: Validation From an Extended Swedish Cohort","authors":"Ella A. Eklund MD ,&nbsp;Sama I. Sayin MD, PhD ,&nbsp;Jonas Smith Jonsson MD ,&nbsp;Hannes van Renswoude MD ,&nbsp;Jan Nyman MD, PhD ,&nbsp;Andreas Hallqvist MD, PhD ,&nbsp;Clotilde Wiel PhD ,&nbsp;Volkan I. Sayin PhD","doi":"10.1016/j.jtocrr.2025.100880","DOIUrl":"10.1016/j.jtocrr.2025.100880","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Immune checkpoint blockade (ICB) is a standard first-line treatment for stage IV NSCLC without actionable oncogenic alterations. &lt;em&gt;KRAS&lt;/em&gt; mutations, prevalent in 30% to 40% lung adenocarcinomas (LUAD) in Western populations, currently lack targeted first-line therapies. This study aimed to assess the predictive value of &lt;em&gt;KRAS&lt;/em&gt; mutations for clinical outcomes after distinct ICB regimens, validating our previous findings in a larger cohort with extended follow-up.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We conducted a retrospective multicenter study including consecutive stage IV LUAD patients (n = 424) treated with either ICB or platinum-doublet chemotherapy between 2016 and 2021 in Western Sweden. Patient demographics, tumor characteristics, treatment details, and survival outcomes were retrospectively collected from patient charts and the Swedish National Lung Cancer Registry. &lt;em&gt;KRAS&lt;/em&gt; mutational status was assessed by next-generation sequencing. Primary end points included overall survival (OS) and progression-free survival (PFS), analyzed using Kaplan-Meier curves and multivariate Cox regression.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Among 424 patients diagnosed with metastatic LUAD, 40% harbored &lt;em&gt;KRAS&lt;/em&gt; mutations (&lt;em&gt;KRAS&lt;/em&gt;&lt;sup&gt;MUT&lt;/sup&gt;). &lt;em&gt;KRAS&lt;/em&gt;&lt;sup&gt;MUT&lt;/sup&gt; patients exhibited significant improvement in OS (16 versus 8 mo, &lt;em&gt;p&lt;/em&gt; &lt; 0.001) and PFS (8 mo versus 5 mo, &lt;em&gt;p&lt;/em&gt; &lt; 0.001) with ICB monotherapy. In contrast, &lt;em&gt;KRAS&lt;/em&gt; wild-type (&lt;em&gt;KRAS&lt;/em&gt;&lt;sup&gt;WT&lt;/sup&gt;) patients derived no survival advantage from ICB monotherapy (OS, 8 mo versus 8 mo, &lt;em&gt;p&lt;/em&gt; = 0.648; PFS 4 mo versus 5 mo, &lt;em&gt;p&lt;/em&gt; = 0.871) although they did so with chemoimmunotherapy (OS, 15 mo versus 8 mo, &lt;em&gt;p&lt;/em&gt; = 0.032; PFS, 6 mo vs 5 mo, &lt;em&gt;p&lt;/em&gt; = 0.033). On multivariate analysis, monotherapy was confirmed as an independent factor improving outcomes in KRAS-mutated patients (hazard ratio [HR] 0.533, 95% confidence interval 0.311-0.912, &lt;em&gt;p&lt;/em&gt; = 0.018). Finally, we identified &lt;em&gt;KRAS&lt;/em&gt;&lt;sup&gt;G12C&lt;/sup&gt; (OS: 13.7 mo versus 10.5 mo, &lt;em&gt;p&lt;/em&gt; = 0.0046, PFS: 7.7 mo versus 6.2 mo, &lt;em&gt;p&lt;/em&gt; = 0.002) and &lt;em&gt;KRAS&lt;/em&gt;&lt;sup&gt;G12V&lt;/sup&gt; (OS: 24.2 mo versus 7.2 mo, &lt;em&gt;p&lt;/em&gt; = 0.0204; PFS: 13.7 mo versus 4.5 mo, &lt;em&gt;p&lt;/em&gt; = 0.063) but not &lt;em&gt;KRAS&lt;/em&gt;&lt;sup&gt;G12D&lt;/sup&gt; (OS, 5.8 mo versus 6.2 mo, &lt;em&gt;p&lt;/em&gt; = 0.777; PFS, 4.6 mo versus 3.2 mo, &lt;em&gt;p&lt;/em&gt; = 0.694) as distinctly and independently predictive of improved survival after receiving ICB-containing treatment.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;&lt;em&gt;KRAS&lt;/em&gt; mutations predict substantial and sustained clinical benefit from first-line ICB monotherapy in metastatic LUAD, whereas &lt;em&gt;KRAS&lt;/em&gt; wild-type patients do not. &lt;em&gt;KRAS&lt;/em&gt;&lt;sup&gt;G12C&lt;/sup&gt; and &lt;em&gt;KRAS&lt;/em&gt;&lt;sup&gt;G12V&lt;/sup&gt; mutations confer improved survival, whereas &lt;em&gt;KRAS&lt;/em&gt;&lt;sup&gt;G12D&lt;/sup&gt; does not. Integrating &lt;em&gt;KRAS&lt;/em&gt; mutation status into clinical practice could","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 10","pages":"Article 100880"},"PeriodicalIF":3.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144920070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Local Ablative Therapy Followed by Osimertinib Rechallenge in Oligoprogressive, EGFR-Mutated NSCLC: A Phase 2 Study","authors":"Azam Ghafoor MD ,&nbsp;Nitin Roper MD ,&nbsp;Chul Kim MD, MPH ,&nbsp;Chuong D. Hoang MD ,&nbsp;Aparna H. Kesarwala MD, PhD ,&nbsp;Kevin A. Camphausen MD ,&nbsp;Kamran Farouq BS ,&nbsp;Elizabeth Akoth RN, BSN, MSN ,&nbsp;Corrine Keen RN, BSN, MS ,&nbsp;Eva Szabo MD ,&nbsp;Hadi Bhageri MD ,&nbsp;Arun Rajan MD ,&nbsp;Udayan Guha MD, PhD","doi":"10.1016/j.jtocrr.2025.100886","DOIUrl":"10.1016/j.jtocrr.2025.100886","url":null,"abstract":"<div><h3>Introduction</h3><div>Osimertinib has exhibited impressive efficacy in advanced EGFR-mutated NSCLC; however, resistance is inevitable. We hypothesized that local ablative therapy (LAT) for oligoprogressive disease (up to five sites), followed by osimertinib rechallenge, would be safe and provide additional second progression-free survival (PFS2) benefit.</div></div><div><h3>Methods</h3><div>This prospective phase 2 trial enrolled <em>EGFR</em>-mutated NSCLC patients in three cohorts: tyrosine kinase inhibitor (TKI)–naive (cohort 1), previously treated with TKI and developed acquired T790M resistance mutation (cohort 2), or previously treated with osimertinib and developed resistance (cohort 3). Patients in cohorts 1 and 2 received upfront osimertinib followed by LAT on oligoprogression, followed by osimertinib rechallenge. Cohort 3 patients underwent LAT on enrollment, followed by osimertinib rechallenge. The primary end points were safety, tolerability, and PFS2 among the patients who underwent LAT across all three cohorts combined. Secondary end points were PFS1 and overall response rates.</div></div><div><h3>Results</h3><div>A total of 37 patients with EGFR-mutated NSCLC were enrolled; 25 in cohort 1, nine in cohort 2, and three in cohort 3. A total of 21 patients received LAT across all three cohorts combined, yielding a median PFS2 of 3.7 months (95% confidence interval: 1.9–4.6 mo) for this population. A subgroup with exceptionally long PFS2 was identified that achieved lower tumor burden and circulating tumor DNA–negative minimal residual disease of the EGFR clone with osimertinib before undergoing LAT. Most adverse events related to LAT were grades 1 and 2.</div></div><div><h3>Conclusions</h3><div>This is the first prospective trial exploring local therapy and osimertinib rechallenge on oligoprogression on osimertinib. Interim analysis revealed that PFS2 in the intention-to-treat patients did not meet its primary goal when compared with historical data on continuation of first-generation EGFR TKIs after LAT. However, definite LAT can be carefully considered in patients using circulating tumor DNA–negative minimal residual disease status as a biomarker for predicting who will benefit from continuation of osimertinib post-LAT.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 10","pages":"Article 100886"},"PeriodicalIF":3.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145096128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complete Response to BET Inhibitor in Primary Pulmonary NUT Carcinoma With Single-Cell Sequencing-Based Analysis: A Case Report","authors":"Zhuomiao Ye MD ,&nbsp;Xin Li PhD ,&nbsp;Minghui Zhang PhD ,&nbsp;Fei Xie MD ,&nbsp;Xiangwen Luo MSc ,&nbsp;Chao Deng MD ,&nbsp;Dan Yang MSc ,&nbsp;Mingzhu Yin PhD","doi":"10.1016/j.jtocrr.2025.100885","DOIUrl":"10.1016/j.jtocrr.2025.100885","url":null,"abstract":"<div><div>NUT carcinoma is a rare and highly aggressive malignancy characterized by rapid progression, resistance to conventional therapies, and an extremely poor prognosis. This report presents a 36-year-old patient with stage IIIB primary pulmonary NUT carcinoma who achieved remarkable clinical outcomes with NHWD-870 monotherapy, a novel BET inhibitor. After just 1 month of treatment, imaging revealed a partial response, and a complete response was achieved within 5 months. Postoperative pathologic examination confirmed no residual cancer cells, and the patient has remained disease-free without recurrence or metastasis to date. To explore the underlying mechanisms of this therapeutic response, single-cell RNA sequencing was performed on the tumor tissue, revealing enhanced activity of immune cells, particularly effector CD8+ T-cells, within the tumor microenvironment. This suggests that NHWD-870 exerts its effects through both direct tumor suppression and modulation of the immune microenvironment. This case highlights the exceptional efficacy of BET inhibitors in the treatment of NUT carcinoma, as evidenced by the first report of complete response achieved with BET inhibitor monotherapy, and supports their potential as a personalized therapeutic strategy.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 10","pages":"Article 100885"},"PeriodicalIF":3.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144919985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term Survival Analysis From PERLA, A Phase II Randomized Trial of Dostarlimab With Chemotherapy Versus Pembrolizumab With Chemotherapy in Metastatic Nonsquamous NSCLC","authors":"Sun Min Lim MD, PhD ,&nbsp;Ana Laura Ortega Granados MD ,&nbsp;Gustavo dix Junqueira Pinto MD, MSc ,&nbsp;Christian Sebastián Fuentes MD ,&nbsp;Giuseppe Lo Russo MD ,&nbsp;Michael Schenker MD ,&nbsp;Jin Seok Ahn MD, PhD ,&nbsp;Filippo de Marinis MD ,&nbsp;Kenneth Locke Jr. PhD ,&nbsp;Zsolt Szijgyarto PhD ,&nbsp;Elena Buss MSc ,&nbsp;Neda Stjepanovic MD, PhD ,&nbsp;Ivan Diaz-Padilla MD, PhD ,&nbsp;Solange Peters MD, PhD","doi":"10.1016/j.jtocrr.2025.100900","DOIUrl":"10.1016/j.jtocrr.2025.100900","url":null,"abstract":"<div><h3>Introduction</h3><div>PERLA is a global, double-blind, phase II trial comparing anti–programmed cell death protein 1 antibodies, dostarlimab, and pembrolizumab in combination with chemotherapy (D+CT and P+CT, respectively) in patients with metastatic nonsquamous NSCLC without actionable genomic aberrations in the first-line setting.</div></div><div><h3>Methods</h3><div>Patients were randomized 1:1 to receive not more than 35 cycles of 500 mg dostarlimab or 200 mg pembrolizumab, with less than or equal to 35 cycles of 500 mg/m² pemetrexed and less than or equal to 4 cycles of cisplatin (75 mg/m²) or carboplatin (area under the curve 5 mg/mL/min) every 3 weeks. The primary end point was the overall response rate by blinded independent central review. The secondary end points included progression-free survival (PFS) on the basis of investigator assessment, overall survival (OS), and safety. Here, we reported on the long-term OS, PFS, and safety analyses.</div></div><div><h3>Results</h3><div>At the end of the study (September 10, 2024), the median follow-up time (mo) for PFS was 30.4 for D+CT and 30.4 for P+CT. The median PFS (mo [95% confidence interval (CI)]) was 8.8 (6.9–11.0) for D+CT and 6.8 (4.9–7.1) for P+CT (hazard ratio 0.77 [95% CI: 0.58–1.03] at 79% maturity). The median follow-up time (mo) for OS was 35.5 for D+CT and 35.2 for P+CT. The median OS (mo [95% CI]) was 20.2 (14.5–27.3) and 15.9 (11.6–19.3), respectively (hazard ratio 0.75 [95% CI: 0.55–1.02] at 70% maturity). Safety profiles were similar between arms and consistent with previous analyses.</div></div><div><h3>Conclusions</h3><div>This long-term analysis reaffirms previous observations that D+CT exhibited similar efficacy to P+CT and exhibits strong clinical efficacy as a first-line treatment for patients with metastatic nonsquamous NSCLC.</div></div><div><h3>Clinical trial registration</h3><div>NCT04581824.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 10","pages":"Article 100900"},"PeriodicalIF":3.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155078","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":"Evaluation of the Safety, Pharmacokinetics, and Antitumor Activity of Tusamitamab Ravtansine in Patients With Nonsquamous NSCLC With High or Moderate Expression of Carcinoembryonic Antigen-Related Cell Adhesion Molecule 5","authors":"Anas Gazzah MD ,&nbsp;Charles Ricordel MD, PhD ,&nbsp;Antoine Italiano MD, PhD ,&nbsp;Byoung Chul Cho MD, PhD ,&nbsp;Emiliano Calvo MD, PhD ,&nbsp;Dong-Wan Kim MD, PhD ,&nbsp;Carole Helissey MD ,&nbsp;Jin-Soo Kim MD, PhD ,&nbsp;Maria Vieito Villar MD ,&nbsp;Francois Ghiringhelli HDR ,&nbsp;Victor Moreno MD, PhD ,&nbsp;Sophie Cousin MD ,&nbsp;Luis Paz-Ares MD, PhD ,&nbsp;Nathalie Fagniez Pharm D ,&nbsp;Mustapha Chadjaa MD ,&nbsp;Anne-Laure Bauchet DECVP, PhD ,&nbsp;Christine Soufflet MD ,&nbsp;Nina Masson MSc ,&nbsp;Fabrice Barlesi MD, PhD","doi":"10.1016/j.jtocrr.2025.100844","DOIUrl":"10.1016/j.jtocrr.2025.100844","url":null,"abstract":"<div><h3>Introduction</h3><div>Tusamitamab ravtansine is an antibody-drug conjugate targeting cells expressing carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) with a maytansinoid payload, DM4. This phase 1b dose-expansion study (NCT02187848) evaluated its safety, pharmacokinetics, and preliminary antitumor activity in patients with nonsquamous NSCLC (NSq NSCLC).</div></div><div><h3>Methods</h3><div>Patients aged above or equal to 18 years with advanced or metastatic NSq NSCLC, life expectancy more than or equal to 12 weeks, and high (≥2+ intensity in ≥50% of tumor cells) or moderate (≥2+ intensity in 1%–49% of tumor cells) CEACAM5 expression (assessed by immunohistochemistry) received intravenous tusamitamab ravtansine 100 mg/m² every 2 weeks.</div></div><div><h3>Results</h3><div>A total of 64 patients with high and 28 with moderate CEACAM5 expression received a median of 8.0 (1–69) and 4.5 (1–38) treatment cycles, respectively. High expressors had 13 confirmed partial responses and 28 stable diseases (objective response rate, 20.3%; 95% confidence interval [CI]: 12.3%–31.7%, <em>p</em> &lt; 0.0001); median duration of response was 6.7 months, and median time to progression was 3.7 months (95% CI: 2.7–5.1 mo). Moderate expressors had two confirmed partial responses (objective response rate, 7.1%; 95% CI: 2.0%–22.7%, <em>p</em> = 0.4117) and 15 stable diseases.</div><div>Treatment-emergent adverse events (AEs) occurred in 78.3% of patients (72/92), 37.0% (34/92) of patients required dose modifications, and 5.4% (5/92) discontinued treatment. The most common treatment-emergent AEs included asthenia (37.0%), keratitis (29.3%), and dyspnea (23.9%). Corneal AEs occurred in 38.0% (35/92), typically grade 1/2, reversible, and manageable by dose modifications.</div></div><div><h3>Conclusions</h3><div>Tusamitamab ravtansine demonstrated a favorable safety profile, objective responses, and antitumor activity in patients with high CEACAM5-expressing NSq NSCLC.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 10","pages":"Article 100844"},"PeriodicalIF":3.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145096129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Associations of Tissue Tumor Mutational Burden and Mutational Status With Clinical Outcomes With Pembrolizumab Plus Chemotherapy Versus Chemotherapy For Metastatic NSCLC [JTO Clinical and Research Reports Vol. 4 No. 1: 100431]","authors":"Marina C. Garassino MD ,&nbsp;Shirish Gadgeel MD ,&nbsp;Silvia Novello MD, PhD ,&nbsp;Balazs Halmos MD ,&nbsp;Enriqueta Felip MD ,&nbsp;Giovanna Speranza MD ,&nbsp;Rina Hui PhD ,&nbsp;Edward B. Garon MD ,&nbsp;Hidehito Horinouchi MD, PhD ,&nbsp;Shunichi Sugawara MD, PhD ,&nbsp;Delvys Rodriguez-Abreu MD, PhD ,&nbsp;Martin Reck MD ,&nbsp;Razvan Cristescu PhD ,&nbsp;Deepti Aurora-Garg PhD ,&nbsp;Andrey Loboda PhD ,&nbsp;Jared Lunceford PhD ,&nbsp;Julie Kobie PhD ,&nbsp;Mark Ayers MS ,&nbsp;Bilal Piperdi MD ,&nbsp;M. Catherine Pietanza MD ,&nbsp;Luis Paz-Ares MD, PhD","doi":"10.1016/j.jtocrr.2025.100892","DOIUrl":"10.1016/j.jtocrr.2025.100892","url":null,"abstract":"","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 10","pages":"Article 100892"},"PeriodicalIF":3.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220590","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":"Lung Cancer in Patients of African Descent: A Transcontinental Review of Epidemiology, Disparities, Outcomes, and Opportunities for Equity in Africa, North America, South America, and the Caribbean","authors":"Elvis Obomanu MD ,&nbsp;Colton Jones MD ,&nbsp;Verna Vanderpuye MD ,&nbsp;Nazik Hammad MD","doi":"10.1016/j.jtocrr.2025.100887","DOIUrl":"10.1016/j.jtocrr.2025.100887","url":null,"abstract":"<div><div>Lung cancer in people of African descent is characterized by transcontinental disparities driven by epidemiologic heterogeneity, systemic inequities, and unequal access to health care. Globally, lung cancer incidence and mortality rates vary; however, underdiagnosis and late-stage presentation in low- and middle-income countries obscure the true prevalence of lung cancer because of limited cancer registries and diagnostic infrastructure. In Africa, most patients with lung cancer present at an advanced stage, primarily because of health illiteracy, misdiagnosis, delayed referrals, and inadequate treatment infrastructure. Although tobacco smoking remains a dominant risk factor worldwide, African populations are disproportionately exposed to environmental and occupational hazards, which substantially elevate their lung cancer risk. In North America, Black people experience disproportionately poor outcomes, including lower rates of lung cancer screening, early diagnosis, surgical intervention, and higher mortality rates compared with their White counterparts. In the Caribbean and South America, Black people continue to face racial infrastructural constraints, racial inequities, and elevated exposure to environmental and occupational carcinogens. Systemic barriers perpetuate these disparities, including limited access to screening, genomic testing, and guideline-concordant therapies.</div><div>Achieving equity in lung cancer outcomes requires strategic initiatives, including the expansion of lung cancer registries in Africa, the Caribbean, and South America, to inform evidence-based interventions. Urgent national and international measures focused on prevention and care for populations of African descent, implementing robust tobacco control policies, addressing systemic and racial inequities, and strengthening health care systems to report and manage lung cancer efficiently are essential steps toward reducing disparities. A transcontinental collaborative approach that includes establishing lung cancer research consortia is vital to share best practices in screening protocols, optimize early detection strategies and treatment, and advocate for policy reforms that address the global burden of lung cancer in populations of African descent.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 10","pages":"Article 100887"},"PeriodicalIF":3.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145096130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-line Selpercatinib or Chemotherapy and Pembrolizumab in Patients From East Asia With RET Fusion–Positive NSCLC: A LIBRETTO-431 Subgroup Analysis","authors":"Koichi Goto MD, PhD ,&nbsp;Herbert H. Loong M.B.B.S. ,&nbsp;Caicun Zhou MD, PhD ,&nbsp;Kazumi Nishino MD, PhD ,&nbsp;Dae Ho Lee MD, PhD ,&nbsp;Se-Hoon Lee MD ,&nbsp;James Chih-Hsin Yang MD, PhD ,&nbsp;Dan Liu PhD ,&nbsp;Minji Kim Uh PhD ,&nbsp;Hongmei Han MS, MAS ,&nbsp;Tarun Puri MD ,&nbsp;Aimee Bence Lin PhD ,&nbsp;Ying Cheng MD","doi":"10.1016/j.jtocrr.2025.100868","DOIUrl":"10.1016/j.jtocrr.2025.100868","url":null,"abstract":"<div><h3>Introduction</h3><div>Selpercatinib’s consistent efficacy and manageable safety profile were observed in patients with <em>RET</em> fusion–positive NSCLC across geographies in single-arm studies (LIBRETTO-001 and LIBRETTO-321). Here, we report the efficacy and safety of the phase 3 study LIBRETTO-431 in patients from East Asia.</div></div><div><h3>Methods</h3><div>LIBRETTO-431 (NCT04194944) is a randomized, open-label phase 3 trial comparing first-line selpercatinib versus pemetrexed and platinum with or without pembrolizumab. Geography (East Asia versus non-East Asia) was a stratification factor. Efficacy end points including progression-free survival (PFS), objective response rate, and duration of response as assessed by means of blinded independent central review were evaluated in patients from East Asia. Pharmacokinetics were assessed in the selpercatinib group. Safety data were collected for all patients who received at least one dose of study treatment.</div></div><div><h3>Results</h3><div>Of the 261 patients enrolled, 142 (54.4%) were from East Asia, with 116 randomized to the intention-to-treat-pembrolizumab population (selpercatinib: n = 75, control: n = 41). With a median follow-up of 19.4 and 21.2 months in the selpercatinib and control groups respectively, the median PFS in patients from East Asia was not yet reached for selpercatinib (95% confidence interval (CI): 16.4–not evaluable) versus 11.1 months (95% CI: 7.0–16.8) for control (hazard ratio: 0.38 [95%CI: 0.22–0.68]; <em>p</em> = 0.0008). Safety and pharmacokinetics were consistent with those previously reported across the development program and adverse events were generally manageable with dose adjustments.</div></div><div><h3>Conclusions</h3><div>Consistent with results in the overall LIBRETTO-431 population, selpercatinib exhibited superior PFS compared with chemotherapy plus pembrolizumab in patients from East Asia with a manageable safety profile. These data further highlight the importance of early comprehensive genomic testing and the use of selpercatinib as a preferred first-line regimen in patients with <em>RET</em> fusion–positive NSCLC across geographies.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 10","pages":"Article 100868"},"PeriodicalIF":3.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144933603","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}