Journal of Clinical Oncology最新文献

{"title":"RINGSIDE Phase II Study of Varegacestat for Treatment of Desmoid Tumors: A Randomized Dose-Finding Clinical Trial.","authors":"Rashmi Chugh, Arun Singh, Vladimir Andelkovic, Atrayee Basu Mallick, Bruce Brockstein, Nam Bui, Sant Chawla, Edwin Choy, Lara E Davis, Mrinal Gounder, Shadi Haddadin, Bernd Kasper, Hyo Song Kim, Alexander Lee, Jeremy Lewin, Nadia Hindi, Prabhjot Mundi, Ravin Ratan, Winette van der Graaf, Janet Yoon, Matthew Birrenkott, Gerald Fetterly, Katie Newhall, Eric Song, Jonathan Yovell, Robin L Jones","doi":"10.1200/JCO-26-00725","DOIUrl":"https://doi.org/10.1200/JCO-26-00725","url":null,"abstract":"<p><strong>Purpose: </strong>Desmoid tumors (DTs) are rare, often locally aggressive, connective tissue neoplasms with limited effective treatment options. We evaluated the safety and efficacy of varegacestat, an oral gamma-secretase inhibitor.</p><p><strong>Methods: </strong>RINGSIDE phase II was an open-label, randomized, dose-finding trial of varegacestat in adults with histologically confirmed DT and disease progression. Participants were randomly assigned 1:1:1 to oral varegacestat 1.2-mg once-daily, 2-mg intermittent (once daily for 2 consecutive days with 5 consecutive days off), or 4-mg intermittent dose. The primary end point was safety. The secondary end point was change in tumor volume from baseline to week 16 per blinded independent central review. At the study end, participants who entered the open-label extension received the selected phase III dose (1.2 mg once daily).</p><p><strong>Results: </strong>In total, 42 participants enrolled in the randomized trial (14 per dose arm). Median varegacestat exposure was 50.5 (range, 3.0-76.0) weeks. Forty-one (97.6%) participants reported treatment-related adverse events (AEs), of which 9 (21.4%) reported grade 3 AEs and none reported serious AEs. There were no grade 4/5 events. The median tumor volume reduction at week 16 was -51.91% for the 1.2-mg once-daily dose, -15.25% for the 2-mg intermittent dose and -9.50% for the 4-mg intermittent dose. The confirmed objective response rate (ORR) was 35.7%, 21.4%, and 21.4%, respectively. Among 29 (69%) participants who entered the open-label extension and received 1.2 mg once daily (median exposure, 102.0 [range, 3.0-169.0] weeks), the median best percent tumor volume change was -85.88% and the confirmed ORR increased to 57.1%.</p><p><strong>Conclusion: </strong>Varegacestat demonstrated clinically meaningful DT volume reduction and ORR with a manageable safety profile across dose regimens. The largest responses were seen with the 1.2-mg once-daily dose, which was selected for the RINGSIDE phase III trial.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2600725"},"PeriodicalIF":44.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136802","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":"Promising but Premature: Rethinking the Evidence From SAKK 06/19.","authors":"Jianguang Miao, Jilin Wu","doi":"10.1200/JCO-26-01804","DOIUrl":"https://doi.org/10.1200/JCO-26-01804","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2601804"},"PeriodicalIF":44.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136760","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":"Time Is Money, but for Whom? The Commodification of Time Toxicity in Oncology.","authors":"Arjun Gupta, Vishal R Patel, Ramy Sedhom, Christopher M Booth","doi":"10.1200/JCO-26-01458","DOIUrl":"https://doi.org/10.1200/JCO-26-01458","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2601458"},"PeriodicalIF":44.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136926","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: \"Promising but Premature: Rethinking the Evidence From SAKK 06/19\" and \"Disentangling Resection From Treatment Response in SAKK 06/19\".","authors":"Richard Cathomas, Stefanie Hayoz, Karin Schäuble, Cyrill A Rentsch","doi":"10.1200/JCO-26-02220","DOIUrl":"https://doi.org/10.1200/JCO-26-02220","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2602220"},"PeriodicalIF":44.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136793","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":"NRG-BR002: A Randomized Phase II/III Trial of Metastasis-Directed Ablation With First-Line Systemic Therapy for Oligometastatic Breast Cancer.","authors":"Steven J Chmura, Kathryn A Winter, Wendy A Woodward, Virginia F Borges, Joseph K Salama, Hania A Al-Hallaq, Martha M Matuszak, Michael T Milano, Nora T Jaskowiak, Reshma Jagsi, Peter Kuhn, Anthony Lucci, Salyna Meas, Stephanie N Shishido, Jeremy Mason, Jose G Bazan, Robert A Nordal, David Y Lee, Benjamin D Smith, Zsolt Gabos, Jason C Ye, Shannon T Kahn, Laura A Vallow, Imran Zoberi, Wajeeha Razaq, Mark V Mishra, Kristin M Lupinacci, Jennifer Moughan, Eleftherios P Mamounas, Julia R White","doi":"10.1200/JCO-26-00201","DOIUrl":"10.1200/JCO-26-00201","url":null,"abstract":"<p><strong>Purpose: </strong>Metastasis-directed therapy is increasingly used for oligometastatic breast cancer, despite its uncertain benefit during first-line systemic therapy. We evaluated whether metastasis-directed ablation improves progression-free survival (PFS) compared with first-line systemic therapy alone in patients with oligometastatic breast cancer.</p><p><strong>Methods: </strong>NRG-BR002 is a randomized phase II/III trial across US/Canadian institutions. Participants had ≤4 metastases, controlled primary disease, ≤12 months of first-line systemic therapy without progression with all visible metastases amenable to stereotactic body radiation therapy (SBRT) or surgical resection and were randomly assigned 1:1 to systemic therapy alone (no ablation) or with metastasis-directed ablation (ablation). The primary end point was PFS, defined as time to progression or death. Secondary end points included overall survival (OS) and toxicity. Circulating tumor cells (CTCs) were evaluated as exploratory biomarkers.</p><p><strong>Results: </strong>From December 2014 to September 2019, 129 patients were enrolled; 125 were eligible for analysis. Median age was 54 years; 79% had hormone receptor-positive, human epidermal growth factor receptor 2‑negative disease, 60% solitary metastasis, 50% bone involvement, and 37% bone only. Ablation was delivered via SBRT for 93%. With 72 PFS events and a median follow-up of 29.9 months, median PFS was 23.0 months (no ablation) versus 19.5 months (ablation; hazard ratio [HR], 0.92 [70% CI, 0.71 to 1.17; 95% CI, 0.57 to 1.47]; one-sided <i>P</i> = .36; stratified <i>P</i> = .42). Thus, the trial did not proceed to phase III. OS did not differ significantly between arms (HR, 1.07 [95% CI, 0.60 to 1.89]; one-sided <i>P</i> = .41; stratified <i>P</i> = .52). No grade 5 toxicities occurred. Exploratory analysis suggested improved PFS with ablation in patients with low or absent pretreatment CTCs.</p><p><strong>Conclusion: </strong>The addition of metastasis-directed ablation added to first-line systemic therapy did not improve PFS or OS in patients with oligometastatic breast cancer. Ablation should not be routinely used outside of clinical trials, except for palliation.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2600201"},"PeriodicalIF":44.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13647293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strengthening Individual-Patient Treatment Prediction in Precision Oncology: The Case for a National Evidence Infrastructure.","authors":"Janet Woodcock, Andrew J Pierce, Charles W Drescher, Jennifer R Leib, Mohsin Saleet Jafri, Daniel J Rader, Jeff Schreier, Julie Ramage, Scott D Ramsey, Robert Dumanois, Diwakar Davar, Aleksandar Mihajlovic, Alice M Giani, Fernanda B Musa, J Felipe Montano-Campos, Maria C M Orr, Megan Anderson Brooks, Linda Emery, Sachia Stonefeld Powell, Giselle Saulnier Sholler, Eric Schadt, Amanda G Paulovich","doi":"10.1200/JCO-26-00797","DOIUrl":"10.1200/JCO-26-00797","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2600797"},"PeriodicalIF":44.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127677","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: Is the Extent of Lymph Node Dissection a Confounder in Perioperative Immunotherapy?","authors":"Fei-Yang Zhang, Run-Cong Nie, Shu-Qiang Yuan","doi":"10.1200/JCO-26-02106","DOIUrl":"https://doi.org/10.1200/JCO-26-02106","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2602106"},"PeriodicalIF":44.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127650","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: If Exercise Were a Pill, We'd All Prescribe It to Patients With Cancer. But It's Not.","authors":"Kathryn H Schmitz, Jennifer A Ligibel","doi":"10.1200/JCO-26-02435","DOIUrl":"https://doi.org/10.1200/JCO-26-02435","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2602435"},"PeriodicalIF":44.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127624","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":"Is the Extent of Lymph Node Dissection a Confounder in Perioperative Immunotherapy?","authors":"Jianming Yang, Bo Wei","doi":"10.1200/JCO-26-01226","DOIUrl":"https://doi.org/10.1200/JCO-26-01226","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2601226"},"PeriodicalIF":44.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127564","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":"Sitagliptin for Acute Graft-Versus-Host Disease Prevention in Alternative Donor Transplantation: A Randomized Phase III Trial","authors":"Man Qiao,Biqi Zhou,Yiyin Chen,Huiying Qiu,Shengli Xue,Ying Wang,Yue Han,Yanming Zhang,Kourong Miao,Jihao Zhou,Miao Miao,Xiao Ma,XiaoJin Wu,Xuefeng He,Xiaohui Hu,Mingming Hu,Han Zhu,Rongxian Wang,Haiping Dai,Tao You,Xiebing Bao,Zaixiang Tang,Xiaofei Yang,Robert Zeiser,Suning Chen,Depei Wu,Yang Xu","doi":"10.1200/jco-26-00670","DOIUrl":"https://doi.org/10.1200/jco-26-00670","url":null,"abstract":"PURPOSE This trial evaluated whether the addition of sitagliptin to antithymocyte globulin (ATG)–based prophylaxis reduces the incidence of acute graft-versus-host disease (aGVHD) after alternative donor hematopoietic stem-cell transplantation. METHODS This prospective, multicenter, open-label, randomized trial enrolled patients age 18-60 years with hematologic malignancies who received myeloablative conditioning haploidentical or unrelated donor transplantation. Participants were randomly assigned in a 1:1 ratio to ATG-based prophylaxis (ATG + calcineurin inhibitor + methotrexate + mycophenolate mofetil) with or without sitagliptin (600 mg orally once every 12 hours, days –1 to +14). The primary end point was the cumulative incidence of grade Ⅱ-Ⅳ aGVHD by day +100. RESULTS From December 22, 2021, to June 16, 2023, 190 of the 251 screened patients were enrolled, with a median follow-up of 29.8 (0.7-41.3) months. The sitagliptin group had a significantly lower incidence of grade Ⅱ-Ⅳ aGVHD on day +100 (14.7% v 31.6%; subdistribution hazard ratio [sHR] = 0.41; P = .005). Reduced grade Ⅲ-Ⅳ (6.3% v 18.9%; sHR = 0.30; P = .010) and intestinal aGVHD (12.6% v 29.5%; P = .004) and superior day +180 GVHD-free, relapse-free survival (GRFS; 86.3% v 72.6%; HR = 0.44; P = .016) were also observed. No between-group disparities were detected in 2-year chronic GVHD, nonrelapse mortality, relapse-free/overall survival, or cytomegalovirus/Epstein-Barr virus reactivation; the adverse event profiles were similar. CONCLUSION In this randomized trial, adjunct sitagliptin to ATG-containing prophylaxis significantly reduced the incidence of grade Ⅱ-Ⅳ aGVHD. Reductions in severe and intestinal aGVHD, as well as improved day +180 GRFS, were exploratory observations; no significant benefits were detected for long-term GRFS, overall survival, or RFS, and treatment did not alter the engraftment, relapse, or infection risk.","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"18 1","pages":""},"PeriodicalIF":45.3,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149092262","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}