Journal of Clinical Oncology最新文献

{"title":"Development and Validation of a Computational Histology Artificial Intelligence-Powered Predictive Biomarker for Selection of Chemotherapy in Advanced Pancreatic Cancer.","authors":"Andrew E Hendifar, Viswesh Krishna, Vrishab Krishna, Haochen Zhang, Asit Tarsode, Vivek Nimgaonkar, Katelyn Smith, Kawther Abdilleh, Snehal Sonawane, Akshay Neema, Ekin Tiu, Brent K Larson, Vladimir Kazarov, Natalie Moshayedi, Shawn Hutchinson, Daniela Bevacqua, Sudheer Doss, Alejandra Alvarez, Drew Watson, Waleed M Abuzeid, Barbara T Grünwald, Marcus Noel, Rashmi Samdani, Dove Keith, Rosalie C Sears, Davendra Sohal, Christos Fountzilas, Grainne M O'Kane, Robert C Grant, Arsen Osipov, Eric A Collisson, Lesli A Kiedrowski, Trevor J Royce, Anirudh R Joshi, Aatur D Singhi, Jennifer J Knox","doi":"10.1200/JCO-25-02199","DOIUrl":"10.1200/JCO-25-02199","url":null,"abstract":"<p><strong>Purpose: </strong>Predictive biomarkers to guide selection of first-line chemotherapy for advanced pancreatic ductal adenocarcinoma (PDAC) are an unmet clinical need. This study used the Computational Histology Artificial Intelligence (CHAI) platform to develop and validate a histomorphology-based G-chemo versus F-chemo (GvF) biomarker that predicts benefit from first-line fluoropyrimidine-based (F-chemo) versus gemcitabine-based (G-chemo) regimens.</p><p><strong>Methods: </strong>The CHAI platform extracted quantitative histomorphologic features from whole-slide images of hematoxylin and eosin-stained diagnostic biopsies. In a multi-institutional development cohort, features associated with differential outcomes as measured by time to next treatment or death (TNTD) between F-chemo-treated and G-chemo-treated patients produced continuous biomarker scores, which were dichotomized into G-pref or F-pref results. The biomarker and threshold were locked. An independent validation cohort from the prospective COMPASS and Know Your Tumor studies assessed differential treatment outcomes by TNTD and overall survival (OS).</p><p><strong>Results: </strong>There were 477 patients (development: 178; validation: 299). In validation, among 173 F-pref patients, those treated with F-chemo had significantly better outcomes than G-chemo for both TNTD (<i>P</i> = .035; median TNTD: F-chemo 8.6 months; G-chemo 7.5 months) and OS (<i>P</i> = .003; median OS: F-chemo 14.4 months; G-chemo 11.7 months). Among 126 G-pref patients, G-chemo had significantly superior TNTD (<i>P</i> = .038; median TNTD: F-chemo 7.2 months; G-chemo 9.6 months), but no difference in OS (<i>P</i> = .5; median OS: F-chemo 12.4 months; G-chemo 14.3 months). In propensity score-weighted analysis, the biomarker predicted treatment effect (biomarker-treatment interaction TNTD <i>P</i> < .001; OS <i>P</i> = .005). RNA subtypes were associated with TNTD and OS but did not predict differential treatment effects (<i>P</i> = .3).</p><p><strong>Conclusion: </strong>The histomorphology-based GvF biomarker predicted differential treatment benefit of first-line GvF. This biomarker can guide optimal treatment selection for first-line therapy in advanced PDAC.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2496-2506"},"PeriodicalIF":44.7,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intismeran Autogene Plus Pembrolizumab Versus Pembrolizumab Alone in High-Risk Resected Melanoma: 5-Year Update of the Randomized Phase IIb KEYNOTE-942 Study.","authors":"Adnan Khattak, Matteo S Carlino, Tarek Meniawy, George Ansstas, Matthew H Taylor, Kevin B Kim, Meredith McKean, Georgina V Long, Ryan J Sullivan, Mark Faries, Thuy T Tran, C Lance Cowey, Andrew Pecora, Theresa Medina, Victoria Atkinson, Clemens Krepler, Thomas Jemielita, Huzhang Mao, Jacky Chow, Laureen S Ojalvo, Janice M Mehnert","doi":"10.1200/JCO-26-00835","DOIUrl":"10.1200/JCO-26-00835","url":null,"abstract":"<p><p>Intismeran autogene (intismeran; formerly V940 or mRNA-4157) is an mRNA-based individualized neoantigen therapy. We report 5-year outcomes of intismeran plus pembrolizumab from the phase IIb KEYNOTE-942 study (ClinicalTrials.gov identifier: NCT03897881). Eligible patients with resected stage IIIB to IV cutaneous melanoma were randomly assigned 2:1 to receive nine doses of intramuscular intismeran 1 mg once every 3 weeks plus 18 doses of intravenous pembrolizumab 200 mg once every 3 weeks or 18 doses of intravenous pembrolizumab 200 mg once every 3 weeks. The primary end point was recurrence-free survival (RFS); secondary end points included distant metastasis-free survival (DMFS) and safety. Five-year analyses were descriptive. Among 157 randomly assigned patients (intismeran plus pembrolizumab, n = 107; pembrolizumab, n = 50), the median planned follow-up at data cutoff (December 15, 2025) was 60.3 (range, 50.5-76.4) months. Intismeran plus pembrolizumab continued to prolong RFS (hazard ratio [HR], 0.510 [95% CI, 0.294 to 0.887) and DMFS (HR, 0.411 [95% CI, 0.200 to 0.843]), with a favorable trend in overall survival (HR, 0.471 [95% CI, 0.165 to 1.345]) versus pembrolizumab. Safety profile continued to be manageable, with no new safety signals. Intismeran plus pembrolizumab was associated with increased T-cell receptor clonality and novel clonotypes versus pembrolizumab; greater novel clone expansion was observed in patients without versus with recurrence in the combination arm. After a 5-year follow-up, intismeran plus pembrolizumab demonstrated sustained, durable treatment benefits versus pembrolizumab alone in resected high-risk melanoma.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2482-2489"},"PeriodicalIF":44.7,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148138120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to: Olaparib in Metastatic Breast Cancer: The Impact of Prior Cyclin-Dependent Kinase 4 and 6 Inhibitor Exposure on Efficacy.","authors":"Nadine M Tung, Tianyu Li, Judy E Garber","doi":"10.1200/JCO-26-00940","DOIUrl":"10.1200/JCO-26-00940","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2558-2560"},"PeriodicalIF":44.7,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148404820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Tumor Genomic Profile on Adjuvant Chemotherapy Efficacy in Resected Pancreatic Adenocarcinoma: Results From the PRODIGE-24/CCTG PA6 Study.","authors":"Andréa Witz, Thierry Conroy, Aurélien Lambert, Julia Salleron, Aboubacar Diallo, Marie Husson, Rémy Nicolle, Pascal Hammel, James Biagi, Daniel J Renouf, Anthony Turpin, Corentin Richard, Jean-Baptiste Bachet, Juan Iovanna, Nelson Dusetti, Laure Monard, Marjorie Mauduit, Jérôme Cros, Alexandre Harlé","doi":"10.1200/JCO-25-02508","DOIUrl":"10.1200/JCO-25-02508","url":null,"abstract":"<p><strong>Purpose: </strong>Modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX/mFFX) is the standard adjuvant chemotherapy for resected pancreatic ductal adenocarcinoma (PDAC), offering survival benefits over gemcitabine (GEM). However, the contribution of molecular biomarkers to treatment selection remains unclear. Here, we characterize the molecular landscape of tumors from the PRODIGE-24/CCTG PA6 trial and assess the clinical impact of genomic alterations and molecular subtypes.</p><p><strong>Patients and methods: </strong>Tumor DNA sequencing was successfully performed in 317/350 tumors (168 mFFX; 149 GEM), complemented by transcriptomic subtyping using the PurIST classifier. Mutational status of four key PDAC driver genes and 24 homologous recombination repair (HRR)-associated genes was analyzed, alongside single-base substitution (SBS) mutational signatures. Primary and secondary end points were disease-free survival (DFS) and cancer-specific survival (CSS), respectively.</p><p><strong>Results: </strong>In the mFFX group, the PurIST subtype was prognostic, with classical tumors showing superior DFS compared with basal-like tumors (stratified hazard ratio [sHR], 0.48 [95% CI, 0.31 to 0.77]). Among <i>KRAS-</i>mutated patients, mFFX significantly improved DFS compared with GEM (sHR, 0.60 [95% CI, 0.45 to 0.79]; <i>P</i> < .001), while no benefit was observed in <i>KRAS</i> wild-type tumors (interaction test, <i>P</i>_int. = 0.010). HRR and <i>BRCA</i> status were not predictive (<i>P</i>_int. = .568 and <i>P</i>_int. = .785, respectively). The benefit of mFFX was consistent across SBS-positive and SBS-negative subgroups.</p><p><strong>Conclusion: </strong>Overall, these results do not support a change in current adjuvant treatment strategies. mFFX remains the standard adjuvant regimen in PDAC, and the observed lack of benefit in <i>KRAS</i> wild-type tumors should be considered hypothesis-generating and warrants further investigation.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2517-2528"},"PeriodicalIF":44.7,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum: Efficacy and Safety of Anselamimab in Immunoglobulin Light Chain Amyloidosis: Results From the Randomized CARES Trials.","authors":"Ashutosh D Wechalekar, Angela Dispenzieri, Vaishali Sanchorawala, Efstathios Kastritis, Divaya Bhutani, Giada Bianchi, Victor H Jimenez-Zepeda, Kenshi Suzuki, Suzanne Lentzsch, Antoine Huart, Alexander Carpinteiro, Eugene Scott Swenson, Zilehuma Khan, Julia Catini, Hrishikesh Kulkarni, Brian Meltzer, Stephen Lake, Michaela Liedtke","doi":"10.1200/JCO-26-01665","DOIUrl":"10.1200/JCO-26-01665","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2563"},"PeriodicalIF":44.7,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Should Artificial Intelligence Direct Systemic Therapy Decisions in Pancreatic Cancer?","authors":"Gabriel A Brooks, Raghav Sundar","doi":"10.1200/JCO-26-00303","DOIUrl":"10.1200/JCO-26-00303","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2467-2470"},"PeriodicalIF":44.7,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148684876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"He Was Always There.","authors":"Vangipuram Sai Shreya","doi":"10.1200/JCO-26-00540","DOIUrl":"10.1200/JCO-26-00540","url":null,"abstract":"<p><p>Not every patient is on the chart-this essay is about learning to see the one who was always there.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2554-2556"},"PeriodicalIF":44.7,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148603476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COMBI-I: Long-Term Overall Survival With Spartalizumab Plus Dabrafenib and Trametinib in <i>BRAF</i> V600-Mutant Advanced Melanoma.","authors":"Antoni Ribas, Caroline Robert, Dirk Schadendorf, Georgina V Long, Hussein Tawbi, Keith Flaherty, Paolo A Ascierto, Paul Nathan, Piotr Rutkowski, Oleg V Leonov, Paul Lorigan, Sorilla Prey, Maristella Saponara, Ana Arance, Caroline Gaudy-Marqueste, Daniil Stroyakovskiy, Celeste Lebbe, Michele Maio, Michele Del Vecchio, Pamela Salman Boghikian, Ralf Gutzmer, Roberta Depenni, Marina Miskic, Mark Russo, Reinhard Dummer","doi":"10.1200/JCO-26-00528","DOIUrl":"10.1200/JCO-26-00528","url":null,"abstract":"<p><p>The COMBI-I trial (ClinicalTrials.gov identifier: NCT02967692) evaluating spartalizumab plus dabrafenib and trametinib (sparta-DabTram, n = 267) versus placebo plus dabrafenib and trametinib (placebo-DabTram, n = 265) for <i>BRAF</i> V600-mutant unresectable or metastatic melanoma failed to reach its primary end point of progression-free survival at 24 months. This final analysis reports overall survival (OS) during at least 5 years of extended follow-up. At the end of the trial (August 21, 2024), the median duration of follow-up was 76.9 months (range, 73.7-83.3 months). The median OS was 61.5 months (95% CI, 41.6 to not evaluable) for the sparta-DabTram arm and 41.6 months (95% CI, 30.6 to 56.9) for the placebo-DabTram arm (hazard ratio, 0.760 [95% CI, 0.598 to 0.966]). The safety findings were consistent with the known safety profile for sparta-DabTram. The most common treatment-related adverse event (TRAE) was pyrexia (65.9% <i>v</i> 46.2%, respectively, in the two study arms). Grade ≥3 TRAEs were reported in 57.3% and 36.7% of patients in the two arms, respectively. The combination of sparta-DabTram appears to improve OS compared with dabrafenib and trametinib alone in patients with <i>BRAF</i> V600-mutant metastatic melanoma.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2490-2495"},"PeriodicalIF":44.7,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148720563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2026.3.2.","authors":"Sonam Puri, Nofisat Ismaila, Ibrahim Hanna Azar, Janet Freeman-Daily, Naoki Furuya, Sara Kuruvilla, Logan Roof, Ana I Velazquez, Yubao Wang, Paul Wheatley Price, Natasha B Leighl","doi":"10.1200/JCO-26-01479","DOIUrl":"10.1200/JCO-26-01479","url":null,"abstract":"<p><p>[Box: see text]<i>Living guidelines are developed for selected topic areas with rapidly evolving evidence that drives frequent change in recommended clinical practice. Living guidelines are updated on a regular schedule by a standing expert panel that systematically reviews the health literature on a continuous basis, as described in the</i> <i>ASCO Guidelines Methodology Manual</i>. <i>ASCO Living Guidelines follow the</i> <i>ASCO Conflict of Interest Policy Implementation for Clinical Practice Guidelines</i><i>. Living Guidelines and updates are not intended to substitute for independent professional judgment of the treating clinician and do not account for individual variation among patients. See appendix for disclaimers and other important information (Appendix 1 and Appendix 2, online only). Updates are published regularly and can be found</i> on <i>the</i> <i>ASCO Publications website</i>.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"e127-e139"},"PeriodicalIF":44.7,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148351643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sustaining High Reliability Amid Artificial Intelligence Adoption in Oncology.","authors":"Shawn Stapleton, Renu Sara Nargund, Caroline Chung","doi":"10.1200/JCO-26-00253","DOIUrl":"10.1200/JCO-26-00253","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2476-2481"},"PeriodicalIF":44.7,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148271633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}