Journal of Clinical Oncology最新文献

{"title":"Azacitidine, Venetoclax, and Revumenib for Newly Diagnosed <i>NPM1</i>-Mutated or <i>KMT2A</i>-Rearranged AML.","authors":"Joshua F Zeidner, Tara L Lin, Rina Li Welkie, Emily Curran, Kristin Koenig, Wendy Stock, Yazan F Madanat, Ronan Swords, Maria R Baer, William Blum, Eytan M Stein, Rebecca L Olin, Gary Schiller, Angela Nichols, Olatoyosi Odenike, Elie Traer, Curtis Lachowiez, Vu H Duong, Michael J Hochman, Sheng F Cai, Catherine Smith, Mona Stefanos, Molly Martycz, Ying Huang, Len Rosenberg, Sonja Marcus, Timothy L Chen, Ashley O Yocum, Brian J Druker, Ross L Levine, Uma Borate, John C Byrd, Alice S Mims","doi":"10.1200/JCO-25-00914","DOIUrl":"https://doi.org/10.1200/JCO-25-00914","url":null,"abstract":"<p><strong>Purpose: </strong>Azacitidine and venetoclax is a standard frontline treatment regimen for newly diagnosed older adults with AML; however, long-term outcomes remain poor. Revumenib is an oral menin inhibitor with clinical activity in AML patients with nucleophosmin-1 mutation (<i>NPM1m</i>) or lysine methyltransferase 2A rearrangements (<i>KMT2Ar</i>).</p><p><strong>Methods: </strong>We conducted a phase I dose-escalation and expansion study of azacitidine, venetoclax, and revumenib at two dose levels (113 mg or 163 mg orally every 12 hours in combination with strong cytochrome P450 inhibitor azoles) in patients aged 60 years and older newly diagnosed with AML with <i>NPM1m</i> or <i>KMT2Ar</i> (ClinicalTrials.gov identifier: NCT03013998).</p><p><strong>Results: </strong>Overall, 43 patients were enrolled and treated. There was no maximal tolerated dose identified. Differentiation syndrome was present in eight (19%) patients and QTc Fridericia prolongation was present in 19 (44%) patients, and neither required permanent discontinuation of revumenib. The overall response rate with an intention-to-treat population was 88.4% (95% CI, 74.9 to 96.1; <i>NPM1m</i>: 85.3%; <i>KMT2Ar</i>: 100%), the rate of composite complete remission (complete remission [CR] + CR with partial or incomplete hematologic recovery) was 81.4% (95% CI, 66.6 to 91.6; NPM1m: 79.4%; KMT2Ar: 88.9%), and the rate of CR was 67.4% (95% CI, 51.5 to 80.9; <i>NPM1m</i>: 65%; <i>KMT2Ar</i>: 78%). No patient had refractory disease after 1-2 cycles of treatment. The median time to first response was 28 days, and 84% of responders achieved remission within the first cycle. All 37 patients evaluated had no evidence of measurable residual disease by a centralized flow cytometry assay.</p><p><strong>Conclusion: </strong>In older adults newly diagnosed with <i>NPM1m</i> or <i>KMT2Ar</i> AML, the combination of azacitidine, venetoclax, and revumenib was able to be safely administered with high rates of CR and clinical activity.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2500914"},"PeriodicalIF":42.1,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144284524","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":"Promoting Reasonable Career Expectations and Maximizing Professional Fulfillment for Academic Oncologists: ASCO Recommendations for Academic Medical Centers.","authors":"Eric P Winer, Laura A Levit, Ethan Basch, Mariana Chavez-MacGregor, Ray Dubois, S Gail Eckhardt, Lee M Ellis, Clifford A Hudis, Deborah Schrag, Corey Speers, Breelyn A Wilky, Michal Tibbits, Rebecca Spence, Elizabeth Garrett-Mayer","doi":"10.1200/JCO-24-02246","DOIUrl":"10.1200/JCO-24-02246","url":null,"abstract":"<p><p>In this statement, ASCO encourages academic medical centers to change their policies and expectations to enhance and promote the professional fulfillment of academic medical oncologists. The statement includes three recommendations directed to academic medical centers to further this goal: (1) establish reasonable clinical workloads for academic medical oncologists, (2) provide resources to enable medical oncologists to participate in and conduct research, and (3) develop and apply their standards for clinical workloads and research support, as well as career advancement and leadership opportunities, fairly and equitably across academic medical oncologists. Overall, improved career satisfaction is likely to result in retention of oncologists in the workforce. This is critical to support high-quality patient care, educate the next generation of cancer-focused professionals, and accelerate research discovering effective strategies for cancer prevention, diagnosis, and treatment.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2017-2023"},"PeriodicalIF":42.1,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390964","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":"Importance of Defining Recurrence in Hepatocellular Carcinoma: Local or Both Local and Other Intrahepatic Recurrences?","authors":"Yuichi Kibe","doi":"10.1200/JCO-24-02861","DOIUrl":"10.1200/JCO-24-02861","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2027-2028"},"PeriodicalIF":42.1,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710051","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":"[¹⁸F]-Labeled Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography in Staging and Restaging Patients With Breast Cancer.","authors":"David Groheux, Sofia C Vaz, Lioe-Fee de Geus-Oei, Elizabeth H Dibble, Gary A Ulaner, Gary J R Cook, Elif Hindié, Philip Poortmans, Ritse M Mann, Heather Jacene, John P Pilkington Woll, Isabel T Rubio, Marie-Jeanne Vrancken Peeters, Stephanie L Graff, Fatima Cardoso","doi":"10.1200/JCO-24-01945","DOIUrl":"10.1200/JCO-24-01945","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1942-1947"},"PeriodicalIF":42.1,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710049","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: Reproducibility of Clinically Meaningful Change in Physical Capacity Tested by Online 6-Minute Walk Test.","authors":"David D Ma, Zhixin Liu, Kimberley Au, Mei Tran, Crisbel M Artuz, Matthew Greenwood, Ian Bilmon, David Kliman","doi":"10.1200/JCO-25-00331","DOIUrl":"10.1200/JCO-25-00331","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2031-2032"},"PeriodicalIF":42.1,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674015","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: Every Patient Is Unique and Deserves the Best: The Present and Future Treatment Landscape of Uncommon Epidermal Growth Factor Receptor Mutations in Non-Small Cell Lung Cancer.","authors":"Derek De-Rui Huang, James Chih-Hsin Yang","doi":"10.1200/JCO-25-00997","DOIUrl":"10.1200/JCO-25-00997","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2033"},"PeriodicalIF":42.1,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007369","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":"Academic Medical Centers and ASCO Recommendations: Starting a Difficult Discussion.","authors":"David P Ryan","doi":"10.1200/JCO-25-00168","DOIUrl":"10.1200/JCO-25-00168","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1939-1941"},"PeriodicalIF":42.1,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811579","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":"Neoadjuvant FOLF(IRIN)OX Chemotherapy for Resectable Pancreatic Adenocarcinoma: A Multicenter Randomized Noncomparative Phase II Trial (PANACHE01 FRENCH08 PRODIGE48 study).","authors":"Lilian Schwarz, Jean-Baptiste Bachet, Aurelia Meurisse, Olivier Bouché, Eric Assenat, Guillaume Piessen, Pascal Hammel, Nicolas Regenet, Julien Taieb, Olivier Turrini, Francois Paye, Anthony Turpin, Francois-Regis Souche, Christophe Laurent, Reza Kianmanesh, Pierre Michel, Dewi Vernerey, Jean-Yves Mabrut, Celia Turco, Stephanie Truant, Antonio Sa Cunha","doi":"10.1200/JCO-24-01378","DOIUrl":"10.1200/JCO-24-01378","url":null,"abstract":"<p><strong>Purpose: </strong>Despite limited RCTs, neoadjuvant chemotherapy (NAC) shows promise for resectable pancreatic adenocarcinoma (rPAC). Few prospective results are available on completing the full therapeutic sequence and oncologic outcomes with NAC.</p><p><strong>Methods: </strong>The PANACHE01-PRODIGE48 phase II trial randomly assigned 153 patients with rPAC (2:2:1) to four cycles of NAC (modified leucovorin, fluorouracil, irinotecan, and oxaliplatin [mFOLFIRINOX], arm 1; leucovorin, fluorouracil, and oxaliplatin [FOLFOX], arm 2) or up-front surgery (control) across 28 French centers (February 2017-July 2020). The primary objective was to evaluate the feasibility and efficacy of these NAC regimens. Two binary primary end points included 1-year overall survival (OS) postrandomization and the rate of patients completing the full therapeutic sequence. Event-free survival (EFS) assessed time to failure, defined as progression before surgery, unresectable/metastatic disease at surgery, recurrence, or death.</p><p><strong>Results: </strong>The primary objective was achieved for arm 1. In the intention-to-treat population, 70.8% (90% CI, 60.8 to 79.6) and 68% (90% CI, 55.5 to 78.8) completed the therapeutic sequence in arm 1 and arm 2, respectively. Within 12 months postrandomization, 84.3% (90% CI, 75.3 to 90.9) and 71.4% (90% CI, 59.0 to 81.8) of the patients were alive in arm 1 and arm 2, respectively. Treatment was safe and well-tolerated in both NAC arms. Arm 2 was stopped after interim analysis for lack of efficacy (H0 rejection for 1-year OS). One-year EFS rates were 51.4% (95% CI, 41.0 to 64.3), 43.1% (95% CI, 31.3 to 59.5), and 38.7% (95% CI, 24.1 to 62.0) in arm 1, arm 2, and control arm, respectively.</p><p><strong>Conclusion: </strong>The feasibility and efficacy of mFOLFIRINOX in the perioperative setting are confirmed concerning therapeutic sequence completion and oncologic outcomes, supporting ongoing trials (PREOPANC3, Alliance AO21806). Further research is needed to identify patients who benefit from NAC (ClinicalTrials.gov identifier: NCT02959879; EudraCT: 2015-001851-65).</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1984-1996"},"PeriodicalIF":42.1,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143784375","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: Importance of Defining Recurrence in Hepatocellular Carcinoma: Local or Both Local and Other Intrahepatic Recurrences?","authors":"Mian Xi, Yizhen Fu, Yaojun Zhang","doi":"10.1200/JCO-25-00327","DOIUrl":"10.1200/JCO-25-00327","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2028-2029"},"PeriodicalIF":42.1,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710054","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":"Novel Postneoadjuvant Prognostic Breast Cancer Staging System.","authors":"David J Winchester, Lavisha Singh, Stephen B Edge, Kimberly H Allison, William E Barlow, Veerle Bossuyt, Mariana Chavez-MacGregor, Emily F Conant, James L Connolly, Jennifer F De Los Santos, Daniel F Hayes, Nola M Hylton, Elizabeth A Mittendorf, Jennifer K Plichta, Elena Provenzano, Kilian E Salerno, Priyanka Sharma, W Fraser Symmans, Donald Weaver, Gabriel N Hortobagyi","doi":"10.1200/JCO-24-01739","DOIUrl":"10.1200/JCO-24-01739","url":null,"abstract":"<p><strong>Purpose: </strong>Prognostic staging after neoadjuvant chemotherapy (NACT) is not included in American Joint Commission on Cancer (AJCC) staging. This study addressed this deficiency by including responses to therapy with standardized staging variables in a validated prognostic staging system for patients treated with NACT.</p><p><strong>Methods: </strong>The National Cancer Database was queried to identify 140,605 patients treated with NACT between 2010 and 2018. Three response categories (no response, partial response, and complete response [pCR]) were created on the basis of comparison of clinical and post-NACT pathologic staging. Univariate and multivariate analyses of clinical stage, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2), and grade were analyzed for each category. Predictive models for each response category were validated using the bootstrap technique. Calibration plots compared predicted and observed 3-year survival probabilities in the training and validation data sets.</p><p><strong>Results: </strong>Each validated model demonstrated statistically significant survival differences in the postneoadjuvant prognostic stage assignment. Of all patients with a pCR, 94.2% were assigned to postneoadjuvant ypStage I compared with 35.5% of patients with no response. Advancing clinical stage had a progressive but small impact on overall survival (OS) with pCR (high-grade, triple-negative breast cancer [TNBC]: cStage I, 97% <i>v</i> cStage IIIB/IIIC, 91%; grade 2 luminal A: 97% <i>v</i> 91%) but was associated with a profound decrease in OS with no response for TNBC or HER2+ disease (high-grade TNBC 89% <i>v</i> 50%) and less profound for grade 2 luminal A disease with no response (97% <i>v</i> 81%).</p><p><strong>Conclusion: </strong>We present a novel, validated prognostic staging system that predicts OS according to the response to NACT. These data will provide AJCC stage assignments for a growing proportion of patients treated with NACT.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1948-1960"},"PeriodicalIF":42.1,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025830","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}