Journal of Clinical Oncology最新文献

{"title":"Zanubrutinib and Venetoclax for Patients With Treatment-Naïve Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma With and Without Del(17p)/<i>TP53</i> Mutation: SEQUOIA Arm D Results.","authors":"Mazyar Shadman, Talha Munir, Shuo Ma, Masa Lasica, Monica Tani, Tadeusz Robak, Ian W Flinn, Jennifer R Brown, Paolo Ghia, Emmanuelle Ferrant, Constantine S Tam, Wojciech Janowski, Wojciech Jurczak, Linlin Xu, Tian Tian, Marcus Lefebure, Stephanie Agresti, Jamie Hirata, Alessandra Tedeschi","doi":"10.1200/JCO-25-00758","DOIUrl":"10.1200/JCO-25-00758","url":null,"abstract":"<p><strong>Purpose: </strong>Several chronic lymphocytic leukemia (CLL) studies have demonstrated promising efficacy with the combination of BCL2 and Bruton tyrosine kinase inhibitors; however, patients with CLL with del(17p) and/or <i>TP53</i> mutation (<i>TP53</i>mut) comprised a small percentage of study populations or were excluded entirely. The purpose of the SEQUOIA Arm D cohort was to evaluate the combination of zanubrutinib + venetoclax in treatment-naïve (TN) patients with CLL/small lymphocytic lymphoma (SLL), in a large population of patients with <i>TP53</i>-aberrant disease.</p><p><strong>Patients and methods: </strong>Arm D is a nonrandomized cohort of patients aged 65 years and older (or 18-64 years with comorbidities). Patients received zanubrutinib from cycle 1 and venetoclax from cycle 4 (ramp-up) to cycle 28, followed by continuous zanubrutinib monotherapy until progressive disease (PD), unacceptable toxicity, or meeting undetectable minimal residual disease (uMRD)-guided stopping criteria.</p><p><strong>Results: </strong>Between November 2019 and July 2022, 114 patients were enrolled: 66 (58%) with <i>TP53</i>-aberrant disease, 47 (41%) without <i>TP53</i>-aberrant disease, and 1 with missing <i>TP53</i> results. At a median follow-up of 31.2 months, 85 patients (75%) remained on zanubrutinib monotherapy; 29 patients (25%) discontinued zanubrutinib because of adverse event, uMRD-guided stopping criteria, PD, or other. In the intention-to-treat population, 59% of patients achieved peripheral blood uMRD. The 24-month progression-free survival estimate was 92% (95% CI, 85% to 96%). The most common any-grade treatment-emergent AEs (TEAEs) were COVID-19 (54%), diarrhea (41%), contusion (32%), and nausea (30%). The most common grade ≥3 TEAEs were neutropenia (17%), hypertension (10%), diarrhea (6%), and decreased neutrophil count (6%).</p><p><strong>Conclusion: </strong>Zanubrutinib + venetoclax demonstrated impressive efficacy and a favorable safety profile in patients with TN CLL/SLL, regardless of the presence of <i>TP53</i>-aberrant disease.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2409-2417"},"PeriodicalIF":42.1,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191863","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":"Zipalertinib in Patients With Epidermal Growth Factor Receptor Exon 20 Insertion-Positive Non-Small Cell Lung Cancer Previously Treated With Platinum-Based Chemotherapy With or Without Amivantamab.","authors":"Zofia Piotrowska, Antonio Passaro, Danny Nguyen, Gerrina Ruiter, Ross A Soo, Victor Ho-Fun Lee, Vamsidhar Velcheti, Daniel Shao-Weng Tan, Se-Hoon Lee, Se Hyun Kim, John Wrangle, James Chih-Hsin Yang, Haruko Daga, Oscar J Juan Vidal, Alexander I Spira, Gonzalo Fernandez-Hinojal, Sang-We Kim, Shigeki Umemura, Mariano Provencio Pulla, Erika K Keeton, Zhihui Sunny Yang, Shengting Li, Zhiying Cindy Xu, Jeffrey A Jones, Helena Alexandra Yu","doi":"10.1200/JCO-25-00763","DOIUrl":"10.1200/JCO-25-00763","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the safety and efficacy of zipalertinib, an irreversible epidermal growth factor receptor (EGFR) inhibitor, in pretreated patients with non-small cell lung cancer (NSCLC) harboring <i>EGFR</i> exon 20 insertion (ex20ins) mutations.</p><p><strong>Methods: </strong>REZILIENT1 (ClinicalTrials.gov identifier: NCT04036682) is a phase I/II open-label trial enrolling patients with locally advanced or metastatic <i>EGFR</i> ex20ins-mutant NSCLC previously treated with platinum-based chemotherapy with/without ex20ins-targeted therapies. Asymptomatic, treated and untreated stable CNS metastases are permitted. We report data from patients treated with zipalertinib 100 mg twice daily. The primary end points are objective response rate (ORR) and duration of response (DOR) by independent central review.</p><p><strong>Results: </strong>At data cutoff (December 10, 2024), 244 patients had received treatment with zipalertinib 100 mg twice daily. The primary efficacy population (8 months' follow-up) comprised patients who had received prior platinum-based chemotherapy without ex20ins-targeted therapy (125 patients), with amivantamab only (30 patients), or with amivantamab and other ex20ins-targeted therapy (21 patients). The confirmed ORR was 35.2% (95% CI, 28.2 to 42.8); median DOR was 8.8 months (95% CI, 8.3 to 12.7). Among patients who received prior platinum-based chemotherapy without ex20ins-targeted therapy, amivantamab only, or amivantamab and other ex20ins-targeted therapy, the confirmed ORR was 40%, 30%, and 14.3%, and median DOR was 8.8, 14.7, and 4.2 months, respectively. Among 68 patients with CNS metastases, the ORR was 30.9%. The most common grade ≥3 treatment-related adverse events were anemia (7%), pneumonitis and rash (2.5% each), and diarrhea, ALT increased, and platelet count decreased (2% each).</p><p><strong>Conclusion: </strong>Zipalertinib demonstrated clinically meaningful efficacy with a manageable safety profile in patients with <i>EGFR</i> ex20ins-mutant NSCLC who received prior platinum-based chemotherapy with or without amivantamab.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2387-2397"},"PeriodicalIF":42.1,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199183","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":"Rewriting Risk: A Data-Driven Look at Myeloma Genetics.","authors":"Krina Patel,Thierry Facon","doi":"10.1200/jco-25-00988","DOIUrl":"https://doi.org/10.1200/jco-25-00988","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"109 1","pages":"JCO2500988"},"PeriodicalIF":45.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661820","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":"Reading the Room: A Joint Perspective From a Scientist- and Patient-Partnered Working Group on the Importance of Patient-Centered Language in the Dissemination of Cancer Research.","authors":"Cara MacInnis,Kyle Dickinson,Kirsten Efremov,Jennifer Coish,Monyse de Nobrega,Jennifer Auchinleck,Isabelle Allain-Labelle,Antonia Palmer,Louise Bird,Shuk On Annie Leung,Julia V Burnier","doi":"10.1200/jco-25-00186","DOIUrl":"https://doi.org/10.1200/jco-25-00186","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"1 1","pages":"JCO2500186"},"PeriodicalIF":45.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661821","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: Sharper Focus, Greater Comfort? Lessons From the ROBOMET Trial.","authors":"Edward Chmiel, Matthias Guckenberger, Erin F Gillespie, Shankar Siva","doi":"10.1200/JCO-25-01560","DOIUrl":"https://doi.org/10.1200/JCO-25-01560","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2501560"},"PeriodicalIF":42.1,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659352","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":"Antibody-Based Therapies for the Treatment of Hodgkin Lymphoma in Older Patients.","authors":"Vivek S Radhakrishnan, Peter W M Johnson","doi":"10.1200/JCO-25-01022","DOIUrl":"https://doi.org/10.1200/JCO-25-01022","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2501022"},"PeriodicalIF":42.1,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659351","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 Without Driver Alterations: ASCO Living Guideline, Version 2025.1.","authors":"Dwight H Owen, Balazs Halmos, Sonam Puri, Angel Qin, Nofisat Ismaila, Fawzi Abu Rous, Krishna Alluri, Janet Freeman-Daily, Narinder Malhotra, Kristen Ashley Marrone, Lyudmila Bazhenova","doi":"10.1200/JCO-25-01062","DOIUrl":"https://doi.org/10.1200/JCO-25-01062","url":null,"abstract":"<p><p><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). Updates are published regularly and can be found at</i> <i>https://ascopubs.org/nsclc-non-da-living-guideline</i>.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2501062"},"PeriodicalIF":42.1,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659355","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":"Positron Emission Tomography-Guided Brentuximab Vedotin, Etoposide, Cyclophosphamide, Doxorubicin, Dacarbazine, and Dexamethasone in Older Patients With Advanced-Stage Classic Hodgkin Lymphoma: A Prospective, Multicenter, Single-Arm, Phase II Cohort of the German Hodgkin Study Group HD21 Trial.","authors":"Justin Ferdinandus, Helen Kaul, Alexander Fosså, Andreas Hüttmann, Felix Keil, Yon-Dschun Ko, Felicitas Hitz, Michaela Schwarz, Corinna Trenker, Andrea Kerkhoff, Peter Staib, Kai Wille, Irmgard Dresel, Dennis Hahn, Bernd Hertenstein, Peter Moosmann, Ulrich Mey, Stefan Balabanov, Tasman Armytage, Fernando Roncolato, Johannes C Hellmuth, Mark Hertzberg, Carsten Kobe, Wolfram Klapper, Christian Baues, Hans-Theodor Eich, Stefanie Kreissl, Michael Fuchs, Janina Jablonski, Gundolf Schneider, Hishan Tharmaseelan, Dennis A Eichenauer, Bastian von Tresckow, Peter Borchmann, Paul J Bröckelmann","doi":"10.1200/JCO-25-00439","DOIUrl":"https://doi.org/10.1200/JCO-25-00439","url":null,"abstract":"<p><strong>Purpose: </strong>Positron emission tomography (PET)-guided therapy with 4-6 cycles of brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone (BrECADD) is highly effective in younger patients with advanced-stage classic Hodgkin lymphoma (AS-cHL). We report feasibility and efficacy of PET-guided BrECADD as first-line treatment in older patients with AS-cHL.</p><p><strong>Patients and methods: </strong>Patients with AS-cHL aged 61-75 years were enrolled in a phase II single-arm cohort of the HD21 trial (ClinicalTrials.gov identifier: NCT02661503). Patients with negative PET/computed tomography after 2×BrECADD (PET2) received a total of 4×BrECADD, while PET2-positive patients received 6×BrECADD. The primary end point was the centrally reviewed complete remission (CR) rate after the end of chemotherapy (EOC). Secondary end points included feasibility, adverse events, treatment-related morbidity (TRMB), progression-free survival (PFS), overall survival (OS), and health-related quality of life (HRQoL).</p><p><strong>Results: </strong>Between June 2020 and April 2023, 85 patients were enrolled, of whom 83 with a median age of 67 years (range, 61-75) were analyzed in the intention-to-treat cohort. Most prevalent ≥grade 3 toxicities included leukopenia (n = 80 [96%]), thrombocytopenia (n = 71 [86%]), anemia (n = 57 [69%]), and febrile neutropenia (n = 46 [55%]). Forty-eight (60%) of 80 patients with centrally reviewed PET2 were scheduled for 4×BrECADD and 32 (40%) for 6×BrECADD. Of these, 71 patients (89%) received the target number of cycles. Sixty-eight patients (82%; 95% CI, 72 to 90) achieved CR at EOC. PFS and OS estimates at 2 years were 91.5% (95% CI, 85 to 98) and 90.8% (95% CI, 84 to 98), respectively. No death was attributed to study treatment. Initially, impaired HRQoL scores improved during follow up and on average reached population reference values.</p><p><strong>Conclusion: </strong>PET-guided BrECADD in older patients is feasible and effective. With a PFS rate on par with that of younger patients, short duration, and limited anthracycline exposure, BrECADD is a valuable treatment option also for older patients with AS-cHL.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2500439"},"PeriodicalIF":42.1,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659353","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 2025.1.","authors":"Joshua E Reuss, Sara Kuruvilla, Nofisat Ismaila, Ibrahim Hanna Azar, Jill Feldman, Naoki Furuya, Paul Wheatley-Price, Logan Roof, Ana I Velazquez, Yubao Wang, Natasha B Leighl","doi":"10.1200/JCO-25-01061","DOIUrl":"https://doi.org/10.1200/JCO-25-01061","url":null,"abstract":"<p><p><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). Updates are published regularly and can be found at</i> <i>https://ascopubs.org/nsclc-da-living-guideline</i>.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2501061"},"PeriodicalIF":42.1,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659354","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":"Guidance for JCO Authors on Subgroup Representation and Reporting.","authors":"Stephanie B Wheeler,Alexia Iasonos,Iona Cheng,Charles Craddock,Kathy D Miller","doi":"10.1200/jco-25-00803","DOIUrl":"https://doi.org/10.1200/jco-25-00803","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"16 1","pages":"JCO2500803"},"PeriodicalIF":45.3,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144640084","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}