JTO Clinical and Research Reports最新文献

{"title":"Dacomitinib With or Without Dose Titration in Treatment-Naive Advanced EGFR-Mutated NSCLC — Primary Analysis of the ATORG-003 Phase 2 Trial","authors":"Aaron C. Tan M.B.B.S., PhD, FRACP, Tae Min Kim MD, Siqin Zhou MSc, Yueh Ni Lim M.B.B.S., Gwo Fuang Ho M.B.B.S., Lye Mun Tho M.B.B.S., Thanyanan Baisamut MD, Naiyarat Prasongsook MD, Suee Lee MD, Sze Huey Tan PhD, Dong-Wan Kim MD, Tony Mok MD, Daniel S.W. Tan M.B.B.S., Herbert H. Loong M.B.B.S.","doi":"10.1016/j.jtocrr.2026.101027","DOIUrl":"10.1016/j.jtocrr.2026.101027","url":null,"abstract":"<div><h3>Introduction</h3><div>Dacomitinib is an approved second-generation EGFR tyrosine kinase inhibitor. In the phase 3 ARCHER 1050 trial, both progression-free survival (PFS) and overall survival (OS) were improved with first-line dacomitinib compared with gefitinib. Post hoc analysis revealed that efficacy (PFS, OS) was similar in both dose-reduced patients and the overall study population. ATORG-003 evaluated a dose-titration strategy to improve tolerability while maintaining efficacy. This is also the first prospective study of dacomitinib’s intracranial efficacy and resistance (tissue and plasma next-generation sequencing).</div></div><div><h3>Methods</h3><div>ATORG-003 (Asian Thoracic Oncology Research Group; five Asian countries) was a single-arm, investigator-initiated phase 2 trial that enrolled patients with treatment-naive stages IIIB to IV <em>EGFR</em>-mutated NSCLC. Patients received dacomitinib 30 mg daily for 4 weeks, with a shared investigator and patient decision for titration to 45 mg in patients with grade less than or equal to 1 toxicity (Common Terminology Criteria for Adverse Events version 5.0). The primary end point was the 12-month PFS rate (in patients without central nervous system metastases only) compared with the historical control. Secondary end points were time to treatment failure (TTF), objective response rate (ORR), OS, intracranial ORR (iORR) and intracranial PFS (iPFS), and safety and tolerability.</div></div><div><h3>Results</h3><div>From September 2019 to October 2022, 118 patients were enrolled. The median age was 65 (range 33–84) years, and 54% were female. <em>EGFR</em> mutation type was exon 19 deletion in 57%, L858R mutation in 42%, and both in 1%. There were 18% of patients who were dose titrated to 45 mg at cycle 2, and 70% tolerated 30 mg (67%) or 45 mg (3%) without dose reduction. The primary end point was met, with a 12-month PFS proportion rate of 59.6% (90% confidence interval [CI]: 50.6%–68.1%) and a 12-month PFS rate of 61.2% (95% CI: 50.5%–70.3%) in the primary analysis cohort. The median PFS was 16.1 months (95% CI: 12.1–19.2), and the median TTF was 19.3 months (95% CI: 16.1–22.1). In the overall study population, the ORR was 77% and the median OS was not reached. In patients with central nervous system metastases (<em>n</em> = 24), the iORR was 54% and the median iPFS was 17.6 months (95% CI: 7.2–23.1). All patients had treatment-related adverse events (TRAEs), with grade 3/4 TRAEs occurring in 25%. The most common grade 3/4 TRAEs were rash (7%), paronychia (4%), and hypokalemia (3%). <em>EGFR</em> T790M resistance was detected in 29 of 96 patients (30%) through plasma next-generation sequencing and in 15 of 29 patients (52%) through tissue next-generation sequencing.</div></div><div><h3>Conclusion</h3><div>ATORG-003 prospectively revealed that dacomitinib with dose titration is a viable strategy in advanced <em>EGFR</em>-mutated NSCLC, maintaining efficacy while improving tolerability.","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 10","pages":"Article 101027"},"PeriodicalIF":3.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149160931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Garsorasib (D-1553) in Combination With Pembrolizumab and Chemotherapy for First-Line Metastatic NSCLC With KRAS G12C Mutation: Results of a Phase 1b Study","authors":"Dong Yan MD,&nbsp;Chaoying Liu MD,&nbsp;Xingya Li MD,&nbsp;Melissa Moore MBBS, PhD,&nbsp;Ruihua Xu MD,&nbsp;Rachel E. Sanborn MD,&nbsp;Shirish M. Gadgeel MD,&nbsp;Michael Millward MD,&nbsp;Zhe Shi MD,&nbsp;Yaolin Wang MD,&nbsp;Kathryn Stazzone BS,&nbsp;Michael J. Chisamore PhD,&nbsp;Ling Zhang MD, PhD","doi":"10.1016/j.jtocrr.2026.101037","DOIUrl":"10.1016/j.jtocrr.2026.101037","url":null,"abstract":"<div><h3>Introduction</h3><div>Garsorasib (D-1553) is an orally administered selective KRAS G12C inhibitor. We report results from group 1 of the phase 1b D1553-101 study assessing garsorasib plus pembrolizumab and platinum-based chemotherapy in participants with <em>KRAS</em> G12C–mutated advanced or metastatic NSCLC.</div></div><div><h3>Methods</h3><div>Eligible participants had locally advanced or metastatic NSCLC with <em>KRAS</em> G12C mutation and were candidates for pembrolizumab plus platinum-based chemotherapy. Participants received garsorasib 600 mg once daily or twice daily combined with pembrolizumab 200 mg once every 3 weeks plus 4 to 6 cycles of cisplatin or carboplatin and pemetrexed (nonsquamous histology) or carboplatin and paclitaxel (squamous histology). The primary end points were safety and the incidence of dose-limiting toxicities (DLTs).</div></div><div><h3>Results</h3><div>As of February 24, 2024, 17 participants received garsorasib 600 mg once daily (<em>n</em> = 10) or twice daily (<em>n</em> = 7) combined with pembrolizumab plus platinum-based chemotherapy. Overall, 94% of participants experienced grade 3 or higher treatment-related adverse events (AEs), and 88% had a dose reduction or interruption due to treatment-related AEs. One participant in the twice-daily group experienced a DLT of grade 2 diarrhea; no other DLTs occurred. Among all participants, the objective response rate was 59%, and the median progression-free survival was 7.4 months.</div></div><div><h3>Conclusion</h3><div>In participants with <em>KRAS</em> G12C–mutated locally advanced or metastatic NSCLC, despite an encouraging signal of efficacy, the incidence of treatment-related AEs with garsorasib plus pembrolizumab and platinum-based chemotherapy was high, and participants frequently had dose modifications or interruptions due to treatment-related AEs. Based on these findings, the study did not proceed to phase 2.</div></div><div><h3>ClinicalTrials.gov identifier</h3><div>NCT04585035.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 10","pages":"Article 101037"},"PeriodicalIF":3.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149212132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integration of Histologic Pattern Classifiers and Graph Convolutional Networks for Prognostic Prediction in Lung Adenocarcinoma","authors":"Yi-Chen Yeh MD, PhD,&nbsp;Wei-Hsiang Yu MS,&nbsp;Min-Shu Hsieh MD, PhD,&nbsp;Fu-Pang Chang MD,&nbsp;Lei-Chi Wang MD, PhD,&nbsp;Chao-Wen Lu MD,&nbsp;Bojan Karlaš PhD,&nbsp;Kun-Hsing Yu MD, PhD,&nbsp;Yu-Chung Wu MD,&nbsp;Jin-Shing Chen MD, PhD,&nbsp;Ming-Sound Tsao MD, PhD,&nbsp;Chao-Yuan Yeh MD,&nbsp;Teh-Ying Chou MD, PhD","doi":"10.1016/j.jtocrr.2026.101017","DOIUrl":"10.1016/j.jtocrr.2026.101017","url":null,"abstract":"<div><h3>Introduction</h3><div>Histologic pattern classification is crucial for diagnosing and prognosticating lung adenocarcinoma, yet its clinical application remains limited by interobserver variability and difficulties in quantifying patterns across whole-slide images (WSIs).</div></div><div><h3>Methods</h3><div>We developed a deep learning–based histologic pattern classifier trained with coarse annotations and implemented through a whole-slide approach. Classification performance was evaluated across five major growth patterns, followed by consensus analysis with expert pathologists. To predict prognosis, we integrated the classifier into a patch-level graph convolutional network (patch-GCN) that aggregated local and global morphologic features across WSIs. Model generalizability was further assessed in two external cohorts.</div></div><div><h3>Results</h3><div>The classifier achieved a mean area under the curve of 0.991 and 90.5% expert model agreement. Consensus analysis revealed strong concordance on typical morphologies but underscored challenges for both experts and the model in regions with atypical histology. The patch-GCN achieved the best prognostic performance (concordance index: 0.789), outperforming models based solely on expert-assessed or model-predicted histologic pattern percentages. Notably, the GCN identified prognostically adverse morphologies, including complex glandular and morule-like patterns, which were not explicitly annotated during training. External validation demonstrated robust generalizability, with concordance indices of 0.654 in the TCGA-LUAD cohort and 0.868 in the NTUH cohort. Model performance depended strongly on pathology-specific feature embeddings.</div></div><div><h3>Conclusion</h3><div>This study demonstrates the feasibility of a WSI-based histologic pattern classifier trained with coarse annotations and establishes a novel GCN-based prognostic framework that enhances predictive accuracy, uncovers clinically relevant morphologies beyond expert labels, and supports granular risk stratification in lung adenocarcinoma.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 9","pages":"Article 101017"},"PeriodicalIF":3.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148855515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pre-treatment Tumor Volume Growth Rate and Baseline Volume Measured by an Artificial Intelligence Program Predict Overall Survival in Patients With Pleural Mesothelioma Undergoing Deferred Systemic Therapy","authors":"Illaa Smesseim MD,&nbsp;Valerio Pugliese,&nbsp;Jacobus Burgers PhD,&nbsp;Kevin Groot Lipman MD, PhD","doi":"10.1016/j.jtocrr.2026.101040","DOIUrl":"10.1016/j.jtocrr.2026.101040","url":null,"abstract":"<div><h3>Introduction</h3><div>The optimal timing of systemic therapy in pleural mesothelioma remains debated, particularly for asymptomatic patients with a limited disease burden. Prior studies suggest that deferred treatment may not compromise overall survival (OS) in selected patients. Reliable prognostic markers to guide treatment timing are lacking. We investigated whether baseline tumor volume and pretreatment tumor growth rate, quantified using an artificial intelligence (AI)–based model, predict OS in patients deferring systemic therapy.</div></div><div><h3>Methods</h3><div>We conducted a single-center retrospective study including patients with pleural mesothelioma diagnosed between 2010 and 2025 who deferred systemic therapy for more than or equal to 3 months and had at least two pretreatment computed tomography scans. Total tumor volume and tumor growth rate (mL/mo) were automatically measured using the AI-based ARTIMES model. Optimal cutoffs were determined using receiver operating characteristic analysis. OS was analyzed using Kaplan–Meier estimates and Cox proportional hazards models.</div></div><div><h3>Results</h3><div>A total of 71 patients were included (median age 66.8 y; 80.3% male; Eastern Cooperative Oncology Group 0–1). The median deferral time was 8.0 months. Optimal cutoffs were 56.5 mL for baseline tumor volume and 67.8 mL/mo for tumor growth rate. Patients with a low baseline tumor volume had a significantly longer median OS compared with those with a high volume (30.95 versus 16.89 mo; <em>p</em> = 0.0066). Similarly, a low tumor growth rate was associated with improved OS (29.40 versus 14.59 mo; <em>p</em> = 0.00057). In multivariable analysis, sarcomatoid histology remained independently associated with worse OS (hazard ratio = 3.28, 95% confidence interval: 1.38–7.75, <em>p</em> = 0.007).</div></div><div><h3>Conclusions</h3><div>AI-derived baseline tumor volume and tumor growth rate are strong prognostic factors for OS in patients with pleural mesothelioma deferring systemic therapy. Patients with low baseline tumor volume and those with low tumor growth rate were significantly associated with a longer OS.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 9","pages":"Article 101040"},"PeriodicalIF":3.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148855514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lung Cancer Screening–Eligible Population From 2000 to 2050 in Argentina: A Simulation Study Brief Report","authors":"M. Victoria Salgado MD, PhD,&nbsp;Jihyoun Jeon PhD,&nbsp;Pianpian Cao PhD,&nbsp;Iris Boyeras MD,&nbsp;Raul Mejia MD, PhD,&nbsp;Rafael Meza PhD","doi":"10.1016/j.jtocrr.2026.101006","DOIUrl":"10.1016/j.jtocrr.2026.101006","url":null,"abstract":"<div><h3>Introduction</h3><div>In Argentina, lung cancer remains the leading cause of cancer death. However, the National Cancer Institute lacks formal lung cancer screening (LCS) recommendations. We projected LCS-eligible populations from 2000 to 2050 under varying screening criteria.</div></div><div><h3>Methods</h3><div>We used Argentina’s version of the Cancer Intervention and Surveillance Modeling Network Smoking History Generator. This microsimulation model generates cohort-specific smoking histories by age and sex. We projected the number of LCS-eligible individuals in Argentina from 2000 to 2050 under (1) the U.S. Preventive Services Task Force 2021 criteria (ages 50–80 y, ≥20 pack-years, currently smoke or have quit within the past 15 y) and (2) the U.S. National Lung Screening Trial criteria (ages 55–74, ≥30 pack-years, currently smoke or have quit within the past 15 y).</div></div><div><h3>Results</h3><div>Under the U.S. Preventive Services Task Force 2021 criteria, LCS-eligible individuals are projected to plateau at 1.6 million between 2018 and 2036, declining to 1.3 million by 2050; the proportion of eligible individuals aged 50 to 80 years is expected to fall from 15.1% in 2018 to 7.8% in 2050 amid population growth and declining smoking rates. Under the National Lung Screening Trial criteria, eligibility peaks at 0.8 million in 2016 and declines to 0.6 million by 2050; the proportion of eligible individuals aged 55 to 74 years decreases from 11.2% to 5.3% over this period.</div></div><div><h3>Conclusions</h3><div>Demand for LCS will gradually decrease as fewer individuals meet the eligibility criteria. Despite projected declines, between 0.5 million and more than 1 million Argentinians will remain LCS eligible by mid-century, supporting consideration of a national screening program to reduce lung cancer mortality.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 9","pages":"Article 101006"},"PeriodicalIF":3.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148855723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EGFR-Mutant Non–Small Cell Lung Cancer With Small Cell Transformation: Clinicopathological Features, Treatment Landscape, and Biomarker Profiles","authors":"Chi-Lu Chiang MD, PhD,&nbsp;Ying-Ting Liao MD,&nbsp;Yi-Chen Yeh MD, PhD,&nbsp;Ruei-Lin Sun MD,&nbsp;Hsu-Ching Huang MD,&nbsp;Yung-Hung Luo MD, PhD,&nbsp;Chia-I Shen MD,&nbsp;Heng-Sheng Chao MD, PhD,&nbsp;Yen-Han Tseng MD, PhD,&nbsp;Tsu-Hui Shiao MD,&nbsp;Ruihong Wang PhD,&nbsp;Haitao Wang PhD,&nbsp;David S. Schrump MD,&nbsp;Yuh-Min Chen MD, PhD","doi":"10.1016/j.jtocrr.2026.101050","DOIUrl":"10.1016/j.jtocrr.2026.101050","url":null,"abstract":"<div><h3>Introduction</h3><div>Transformed small-cell lung cancer (tSCLC) is a clinically important resistance mechanism to EGFR tyrosine kinase inhibitors in <em>EGFR</em>-mutant non–small cell lung cancer. This study characterizes clinical features, treatment outcomes, and biomarker profiles in patients with tSCLC.</div></div><div><h3>Methods</h3><div>Data from 45 patients with <em>EGFR</em>-mutant NSCLC who developed tSCLC between 2014 and 2023 were analyzed. Demographic characteristics, treatment histories, and delta-like ligand 3 (DLL3) and B7-H3 expression were collected. Objective response rate, progression-free survival (PFS), and posttransformation survival (PTS) were assessed. Spatial transcriptomic profiling was performed in selected cases.</div></div><div><h3>Results</h3><div>Most patients were women (60%) and never-smokers (75.6%). Exon 19 deletion was the predominant <em>EGFR</em> mutation (57.8%). Median PFS and PTS were 3.3 and 9.2 months, respectively. Etoposide plus platinum (EP) was the predominant first-line regimen (69.8%), with 23.2% of the patients receiving EP plus immune checkpoint or tyrosine kinase inhibitors. EP-based combination regimens yielded a numerically higher objective response rate and a significantly longer PFS than EP alone (7.5 versus 2.8 months, <em>p</em> = 0.002). PTS was longer with EP-based regimens than with other regimens (10.4 versus 6.4 months, <em>p</em> = 0.035). DLL3 and B7-H3 were expressed in 87.5% and 66.7% of tumors, respectively, without prognostic significance. Multivariable analysis identified brain metastasis and liver progression at transformation as adverse prognostic factors. Spatial transcriptomic analysis revealed neuroendocrine lineage reprogramming, stromal depletion, and immune exclusion.</div></div><div><h3>Conclusions</h3><div>tSCLC remains an aggressive resistance phenotype with poor outcomes. EP-based combination strategies may provide clinical benefit, whereas frequent DLL3 expression supports further evaluation of targeted therapies.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 9","pages":"Article 101050"},"PeriodicalIF":3.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148855516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Long-Term Survival Between Nivolumab Plus Ipilimumab and Nivolumab Plus Ipilimumab With Chemotherapy in Advanced NSCLC: A Multicenter Retrospective Cohort Study","authors":"Kiyohide Komuta MD,&nbsp;Kinnosuke Matsumoto MD,&nbsp;Motohiro Tamiya MD,&nbsp;Takayuki Shiroyama MD, PhD,&nbsp;Yuhei Kinehara MD, PhD,&nbsp;Akihiro Tamiya MD,&nbsp;Tomoki Kuge MD,&nbsp;Junji Uchida MD, PhD,&nbsp;Hidekazu Suzuki MD,&nbsp;Suguru Yamamoto MD, PhD,&nbsp;Satoshi Tobita MD,&nbsp;Toshie Niki MD, PhD,&nbsp;Satoshi Tetsumoto MD, PhD,&nbsp;Osamu Morimura MD, PhD,&nbsp;Akio Osa MD, PhD,&nbsp;Toshiyuki Minami MD, PhD,&nbsp;Kazumi Nishino MD, PhD,&nbsp;Yoshito Takeda MD, PhD,&nbsp;Atsushi Kumanogoh MD, PhD","doi":"10.1016/j.jtocrr.2026.101048","DOIUrl":"10.1016/j.jtocrr.2026.101048","url":null,"abstract":"<div><h3>Introduction</h3><div>Pivotal clinical trials have reported the survival benefits of both nivolumab plus ipilimumab (NI) and nivolumab plus ipilimumab with 2 cycles of platinum-based chemotherapy (NICT) compared with chemotherapy. However, real-world evidence comparing NI and NICT with long-term follow-up remains limited.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed 181 patients treated with NICT or NI across 13 institutions in Japan. The primary end points were median overall survival (OS) and the 36-month OS rate. Secondary end points included progression-free survival (PFS), objective response rate, disease control rate, and treatment-related adverse events (TRAEs). To reduce treatment-selection bias, 1:1 propensity score matching was performed using 11 covariates.</div></div><div><h3>Results</h3><div>In the post–propensity score matching cohort (47 pairs; n = 94; median follow-up, 42.6 and 44.1 months), the median PFS was 8.7 months with NICT versus 4.7 months with NI (hazard ratio [HR] 0.86; <em>p</em> = 0.51). The median OS was 19.5 months with NICT versus 16.3 months with NI (HR 0.79; <em>p</em> = 0.37), with similar 36-month OS rates (34.3% versus 30.9%). The objective response rate was significantly higher with NICT than with NI (68.1% versus 34.0%) (<em>p</em> = 0.002), as was the disease control rate (83.0% versus 53.2%) (<em>p</em> = 0.004). NICT was associated with a higher cumulative incidence of TRAEs of grade 3 or higher (HR 2.25 [95% confidence interval, 1.03–4.91]) (Gray’s test <em>p</em> = 0.039). Treatment discontinuation and treatment-related deaths were comparable between the groups.</div></div><div><h3>Conclusions</h3><div>With more than 40 months of follow-up, NICT was associated with higher response rates and a higher incidence of TRAEs of grade 3 or higher than NI, without a clear PFS or OS advantage. Adding 2-cycles of chemotherapy may enhance early disease control but at the cost of increased toxicity, and this balance should be considered when selecting treatment for patients for whom tolerability is a major concern.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 9","pages":"Article 101048"},"PeriodicalIF":3.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148855722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RATIONALE-303: Long-Term Outcomes of Tislelizumab in Previously Treated Advanced/Metastatic NSCLC","authors":"Pedro de Marchi MD,&nbsp;Yun Fan MD,&nbsp;Zhiyong Ma MD,&nbsp;Yan Wang MD,&nbsp;Yuanyuan Bao MS,&nbsp;Wenjuan Zheng MD,&nbsp;Kirsha Naicker PhD,&nbsp;Caicun Zhou MD","doi":"10.1016/j.jtocrr.2026.101028","DOIUrl":"10.1016/j.jtocrr.2026.101028","url":null,"abstract":"<div><h3>Introduction</h3><div>RATIONALE-303 (NCT03358875) investigated the efficacy and safety of tislelizumab versus docetaxel in pretreated patients with advanced NSCLC. We present long-term outcomes with an additional 30-month follow-up after the final analysis.</div></div><div><h3>Methods</h3><div>In this open-label, randomized, phase 3 trial, patients aged 18 years or older with locally advanced or metastatic NSCLC that progressed on prior platinum-based chemotherapy were randomized (2:1) to tislelizumab or docetaxel. The dual primary end points were overall survival (OS) in the intent-to-treat (ITT) population and OS in patients with programmed death-ligand 1 (PD-L1) tumor cell expression 25% or greater. Secondary end points included progression-free survival (PFS), objective response rate (ORR), duration of response (DoR), and safety.</div></div><div><h3>Results</h3><div>A total of 805 patients were randomized (ITT: tislelizumab, <em>n</em> = 535, docetaxel, <em>n</em> = 270; PD-L1 ≥ 25%: tislelizumab, <em>n</em> = 227, docetaxel, <em>n</em> = 115). At the data cutoff (January 18, 2024), the median OS follow-up was 46.5 months (tislelizumab) and 41.0 months (docetaxel). The median OS was 16.9 versus 11.9 months (stratified hazard ratio [HR] = 0.67; 95% confidence interval [CI]: 0.57–0.80) and 19.3 versus 11.5 months (stratified HR = 0.52; 95% CI: 0.40–0.68) for tislelizumab versus docetaxel in the ITT and PD-L1 25% or greater populations, respectively. In the ITT population, tislelizumab showed improved PFS (median 4.2 versus 2.6 mo; HR = 0.64; 95% CI: 0.54–0.76), a higher ORR (22.6% versus 7.8%), and a longer DoR (median 13.5 versus 6.1 mo) than docetaxel. Grade 3 or higher treatment-related adverse events were less frequent with tislelizumab than with docetaxel (16.1% versus 66.3%). No new safety signals were identified.</div></div><div><h3>Conclusions</h3><div>Extended follow-up confirmed clinically meaningful improvements in OS and other efficacy outcomes with tislelizumab versus docetaxel in previously treated advanced/metastatic NSCLC, with a favorable safety profile.</div></div><div><h3>Clinical trial registration</h3><div>NCT03358875</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 8","pages":"Article 101028"},"PeriodicalIF":3.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13416824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Treatment Outcomes Across Actionable Genomic Alterations in NSCLC: A Large Multicenter Real-World Study","authors":"Yasuhiro Kato MD, PhD,&nbsp;Nobuhiko Nishijima MD, PhD,&nbsp;Satoshi Takahashi MD, PhD,&nbsp;Yukari Shirakura MD,&nbsp;Miwako Omori MD, PhD,&nbsp;Maiko Asai MD,&nbsp;Aya Fukuizumi MD, PhD,&nbsp;Kakeru Hisakane MD, PhD,&nbsp;Shinji Nakamichi MD, PhD,&nbsp;Susumu Takeuchi MD, PhD,&nbsp;Akihiko Miyanaga MD, PhD,&nbsp;Yoshinobu Saito MD, PhD,&nbsp;Takashi Hirose MD,&nbsp;Yukio Hosomi MD, PhD,&nbsp;Kazuo Kasahara MD, PhD,&nbsp;Masahiro Seike MD, PhD,&nbsp;Tetsuya Okano MD, PhD,&nbsp;East Japan Chesters Group","doi":"10.1016/j.jtocrr.2026.101020","DOIUrl":"10.1016/j.jtocrr.2026.101020","url":null,"abstract":"<div><h3>Introduction</h3><div>Although the efficacy of molecular targeted therapies varies across actionable genomic alterations in NSCLC, comparisons within a single real-world cohort remain limited.</div></div><div><h3>Methods</h3><div>We conducted a retrospective multi-institutional study of 810 consecutive Japanese patients with advanced or recurrent NSCLC harboring actionable genomic alterations who received molecular targeted therapy from 2017 to 2023. Patients were classified into the following three genomic groups: <em>EGFR</em> mutations (group A), <em>ALK</em>/<em>ROS1</em>/<em>RET</em> fusion oncogenes (group B), and others, including <em>MET</em> exon 14 skipping, <em>BRAF V600E</em>, and <em>KRAS G12C</em> mutations (group C). Treatment efficacy and safety were compared across the groups.</div></div><div><h3>Results</h3><div>Treatment outcomes differed between the subgroups. Group B demonstrated the highest objective response rate (85.8%) and the longest median real-world progression-free survival (rwPFS; 42.5 mo); median overall survival (OS) was not reached. Group A had intermediate outcomes. Group C exhibited the shortest rwPFS (9.2 mo), poorer OS, and higher rates of treatment discontinuation due to adverse events. Such hierarchical differences were observed in patients with baseline central nervous system metastases and in those receiving first-line treatment. In multivariate analysis, genomic subgroup remained associated with rwPFS and OS, with fusion-driven tumors maintaining superior outcomes irrespective of other factors.</div></div><div><h3>Conclusions</h3><div>This large real-world analysis yielded a hierarchy of therapeutic benefits across actionable genomic alterations in NSCLC. Patients with fusion-driven tumors benefited from targeted therapy, whereas those with <em>EGFR</em>-mutated tumors had intermediate outcomes. Treatment of patients with <em>MET</em> exon 14 skipping, <em>BRAF V600E</em>, and <em>KRAS G12C</em> mutations had limited efficacy and higher toxicity, underscoring the need for improved therapeutic strategies.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 8","pages":"Article 101020"},"PeriodicalIF":3.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148637265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Response","authors":"Elio Adib MD,&nbsp;Amin H. Nassar MD,&nbsp;Florence K. Keane MD","doi":"10.1016/j.jtocrr.2026.101031","DOIUrl":"10.1016/j.jtocrr.2026.101031","url":null,"abstract":"","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 8","pages":"Article 101031"},"PeriodicalIF":3.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148730981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}