Journal of Clinical Oncology最新文献

{"title":"Investigating Racial and Ethnic Disparities Along the Care Cascade for Older Adults Newly Diagnosed With Metastatic Cancer.","authors":"Jennifer L Lund, Vanessa E Slater, Allison Magnuson","doi":"10.1200/JCO-25-01613","DOIUrl":"10.1200/JCO-25-01613","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"3233-3236"},"PeriodicalIF":41.9,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955877","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: PASS-01: Randomized Phase II Trial of Modified FOLFIRINOX Versus Gemcitabine/Nab-Paclitaxel and Molecular Correlatives for Previously Untreated Metastatic Pancreatic Cancer.","authors":"Jennifer J Knox, Grainne O'Kane, Daniel King, Daniel Laheru, Amber N Habowski, Kenneth Yu, Kimberly Perez, Andrew J Aguirre, Zachary Coyne, Harry Harvey, Ronan A McLaughlin, Raymond W Jang, Robert C Grant, Elena C Elimova, Daniel J Renouf, Sandra Fischer, Kai Duan, Stephanie Ramotar, Gun Ho Jang, Amy Zhang, Craig E Devoe, Harshabad Singh, Michael J Pishvaian, Fieke E M Froeling, Muhammad W Saif, Eileen M O'Reilly, Erica S Tsang, Brian M Wolpin, Julie M Wilson, Anna Dodd, Trevor J Pugh, Xiang Y Ye, Steven Gallinger, David A Tuveson, Faiyaz Notta, Elizabeth M Jaffee","doi":"10.1200/JCO-25-02195","DOIUrl":"10.1200/JCO-25-02195","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"3325"},"PeriodicalIF":41.9,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137512","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":"Rethinking Treatment Priorities in Estrogen Receptor-Low Breast Cancer.","authors":"Jincong Q Freeman, Rita Nanda, Frederick M Howard","doi":"10.1200/JCO-25-01176","DOIUrl":"10.1200/JCO-25-01176","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"3322-3323"},"PeriodicalIF":41.9,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12527746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955794","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":"Efficacy and Safety of Long-Term Continuous Nirogacestat Treatment in Adults With Desmoid Tumors: Results From the DeFi Trial.","authors":"Ravin Ratan,Bernd Kasper,Thierry Alcindor,Patrick Schöffski,Winette T A van der Graaf,Noah Federman,Nam Q Bui,Gina D'Amato,Richard F Riedel,Steven Attia,Sant Chawla,Allison Lim,Brad Tumminello,Ana B Oton,Yucheng Chu,Shengfan Zhou,Mrinal Gounder","doi":"10.1200/jco-25-00582","DOIUrl":"https://doi.org/10.1200/jco-25-00582","url":null,"abstract":"In the phase III placebo-controlled DeFi trial (ClinicalTrials.gov identifier: NCT03785964) primary analysis, nirogacestat showed significant improvement versus placebo in progression-free survival (PFS), objective response rate (ORR), and patient-reported outcomes (PRO) in adult patients with progressing desmoid tumors (DT; median [range] exposure: 20.6 [0.3-33.6] months). Here, long-term nirogacestat efficacy and safety were evaluated in patients randomly assigned to nirogacestat and followed through the final data cutoff date of December 19, 2024. End points included PFS and ORR per RECIST v1.1, PRO, and safety. The median (range) duration of exposure was 33.6 (0.3-61.8) months. Median PFS was not reached. The ORR with up to 4 years of nirogacestat treatment was 45.7% (32 of 70), with three additional partial and three additional complete responses since the primary analysis. Further target tumor size reduction occurred in most patients. Benefits in PROs were sustained while on treatment. Frequently reported treatment-emergent adverse events (TEAEs) decreased in incidence and severity over time. Since the primary analysis, four patients discontinued nirogacestat because of TEAEs between years 2 and 4. In conclusion, long-term continuous nirogacestat treatment was associated with further tumor size reductions, durable objective responses, sustained PRO benefits, and a manageable safety profile consistent with the primary analysis.","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"1 1","pages":"JCO2500582"},"PeriodicalIF":45.3,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145331857","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":"Why Adjuvant Treatment With a CDK4/6 Inhibitor Should Be Recommended for Women With High-Risk Breast Cancer: Methodologic Considerations on Available Evidence.","authors":"Fabio Conforti, Federico Merlo, Laura Pala, Jacopo Canzian, Benedetta Tinterri, Tommaso De Pas, Marzia Locatelli, James C Dickerson, Javier Cortes, Dennis J Slamon, Richard Gelber, Vincenzo Bagnardi","doi":"10.1200/JCO-25-01148","DOIUrl":"10.1200/JCO-25-01148","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"3237-3244"},"PeriodicalIF":41.9,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080941","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":"CDK4/6 Inhibitors in Estrogen Receptor-Low Breast Cancer.","authors":"Yakup Ergun","doi":"10.1200/JCO-25-00836","DOIUrl":"10.1200/JCO-25-00836","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"3321"},"PeriodicalIF":41.9,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955828","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":"Efficacy and Safety of Glofitamab Plus Polatuzumab Vedotin in Relapsed/Refractory Large B-Cell Lymphoma Including High-Grade B-Cell Lymphoma: Results From a Phase Ib/II Trial.","authors":"Martin Hutchings,Anna Sureda,Francesc Bosch,Thomas Stauffer Larsen,Paolo Corradini,Abraham Avigdor,María José Terol,Antonio Rueda Dominguez,Antonio Pinto,Alan Skarbnik,Raul Cordoba,Judit Meszaros Jørgensen,Pier Luigi Zinzani,Wilfred Leung,Alessia Bottos,Donghang Li,James Relf,Maneesh Tandon,Gila Sellam,Giuseppe Gritti","doi":"10.1200/jco-25-00992","DOIUrl":"https://doi.org/10.1200/jco-25-00992","url":null,"abstract":"PURPOSEAn unmet need remains for more effective therapies for relapsed/refractory (R/R) large B-cell lymphoma (LBCL), especially high-grade B-cell lymphoma (HGBCL). We present the primary analysis of a phase Ib/II study (ClinicalTrials.gov identifier: NCT03533283) investigating efficacy and safety of glofitamab plus polatuzumab vedotin (Glofit-Pola) in patients with R/R LBCL, including HGBCL and those who received previous chimeric antigen receptor (CAR) T-cell therapy.METHODSPatients received 1,000 mg obinutuzumab on Cycle (C)1 Day (D)1 (once daily). Polatuzumab vedotin (1.8 mg/kg) was given on C1D2 and D1 of C2-6 (21-day cycles; once daily). Glofitamab was given as step-up doses in C1 (D8, 2.5 mg; D15, 10 mg) followed by 30 mg on D1 of C2-12 (21-day cycles; once daily). Polatuzumab vedotin was given for six fixed-duration cycles, and glofitamab for 12.RESULTSAs of September 2, 2024, 129 patients with LBCL (HGBCL; n = 44, 34.1%), received ≥1 dose of study treatment. The median age was 67 years (range, 23-84), and 63.6% were male. Patients had received a median of 2 (range, 1-7) previous lines of treatment (previous CAR T-cell therapy, n = 28, 21.7%). The independent review committee-assessed overall response rate was 78.3% (complete response rate, 59.7%). The median progression-free survival and overall survival (OS) were 12.3 and 33.8 months, respectively (median OS follow-up time, 32.7 months). The most common adverse event (AE) was cytokine release syndrome (43.4%; grade 1-2: 41.9%; one grade 5 event). Grade 3-4 AEs occurred in 58.9% of patients; 9.3% had grade 5 AEs, and 14.7% discontinued treatment because of AEs.CONCLUSIONGlofit-Pola demonstrated high efficacy and durable responses, with manageable safety, in heavily pretreated patients with R/R LBCL, including patients with HGBCL and previous CAR T-cell therapy failure.","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"15 1","pages":"JCO2500992"},"PeriodicalIF":45.3,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145331859","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":"Updated Overall Survival Analysis From the Phase 2 PHAROS Study of Encorafenib Plus Binimetinib in Patients With BRAF V600E-Mutant Metastatic Non-Small Cell Lung Cancer.","authors":"Melissa L Johnson,Egbert F Smit,Enriqueta Felip,Suresh S Ramalingam,Myung-Ju Ahn,Anne Tsao,Bruce E Johnson,Michael Offin,Maen Hussein,Ibiayi Dagogo-Jack,Jonathan W Goldman,Jeffrey M Clarke,Marcelo V Negrao,Rachel E Sanborn,Daniel Morgensztern,Tiziana Usari,Keith Wilner,Linh Alejandro,Nada Rifi,Xiaosong Zhang,Gregory J Riely","doi":"10.1200/jco-25-02023","DOIUrl":"https://doi.org/10.1200/jco-25-02023","url":null,"abstract":"The phase 2 PHAROS study previously showed that encorafenib plus binimetinib has antitumor activity in patients with BRAF V600E-mutant metastatic non-small cell lung cancer (mNSCLC). In PHAROS, 98 patients (59 treatment naïve; 39 previously treated) received encorafenib 450 mg once daily and binimetinib 45 mg twice daily. We report updated results from data cutoff of March 14, 2025. The median duration of treatment with both encorafenib and binimetinib was 16.3 months in treatment-naïve and 5.5 months in previously treated patients. After median follow-up for OS of 52.3 months in treatment-naïve patients, mOS was 47.6 months (95% CI, 31.3 to not estimable); 4-year OS probability was 49% (95% CI, 35 to 62). After median follow-up for OS of 48.2 months in previously treated patients, mOS was 22.7 months (95% CI, 14.1 to 32.6); 4-year OS probability was 31% (95% CI, 16 to 47). In treatment-naïve and previously treated groups, 58% and 26% received ≥1 subsequent systemic anticancer treatment, respectively. Safety profile remained consistent with that in prior analyses. While comparisons across trials should be done cautiously, encorafenib plus binimetinib was associated with the the longest mOS reported to date with targeted treatment in patients with treatment-naïve BRAF V600E-mutant mNSCLC.","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"352 1","pages":"101200JCO2502023"},"PeriodicalIF":45.3,"publicationDate":"2025-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145314596","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":"Five-Year Follow-Up Analysis of ZUMA-5: Axicabtagene Ciloleucel in Relapsed/Refractory Indolent Non-Hodgkin Lymphoma.","authors":"Sattva S Neelapu,Julio C Chavez,Alison R Sehgal,Narendranath Epperla,Matthew L Ulrickson,Emmanuel Bachy,Pashna N Munshi,Carla Casulo,David G Maloney,Sven de Vos,Ran Reshef,Lori A Leslie,Olalekan O Oluwole,Ibrahim Yakoub-Agha,Rashmi Khanal,Joseph D Rosenblatt,Jacob Wulff,Rhine R Shen,Wangshu Zhang,Soumya Poddar,Harry Miao,Olga Nikolajeva,Caron A Jacobson","doi":"10.1200/jco-25-00668","DOIUrl":"https://doi.org/10.1200/jco-25-00668","url":null,"abstract":"Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) follicular lymphoma (FL). Here, we report updated clinical outcomes from ZUMA-5 in 159 enrolled patients with R/R indolent non-Hodgkin lymphoma (iNHL; 127 with FL and 31 with marginal zone lymphoma) after a median follow-up of 64.6 months. Patients underwent leukapheresis and received lymphodepleting chemotherapy and axi-cel (2 × 106 CAR T cells/kg). The overall response rate was 90% (75% complete response rate). The median duration of response was 60.4 months, and the median progression-free survival (PFS) was 62.2 months; median time to next treatment and overall survival were not reached (NR). At data cutoff, 55% of patients were alive without requiring subsequent anticancer therapy. Median lymphoma-specific PFS in patients with FL was NR; 34% had progression or death due to lymphoma or study treatment. Notably, after 30 months postinfusion, progression or lymphoma-related deaths were rare. Late-onset toxicities were infrequent and largely unrelated to axi-cel. Durable response and prolonged survival in FL were associated with robust early CAR T-cell expansion and naïve product phenotype. These findings confirm sustained responses and manageable safety with axi-cel in the long term among patients with R/R iNHL and its potential as a curative therapy in FL.","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"101 1","pages":"JCO2500668"},"PeriodicalIF":45.3,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305509","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":"Ruxolitinib Versus Best Available Therapy in Patients With Steroid-Refractory Acute Graft-Versus-Host Disease: Final Analysis From the Randomized Phase III REACH2 Trial.","authors":"Mohamad Mohty, Gerard Socié, Jeff Szer, Dietger Niederwieser, Jason Butler, Eva Wagner-Drouet, Reuven Or, Tsila Rovenvald-Zuckerman, Sinem Civriz Bozdag, Edouard Forcade, Giovanni Grillo, Nicolaus Kröger, Friedrich Stölzel, Domenico Russo, Jaime Sanz, Rajendra Sarkar, Tommaso Stefanelli, Celine Wilke, Robert Zeiser, Nikolas von Bubnoff","doi":"10.1200/JCO-25-00809","DOIUrl":"https://doi.org/10.1200/JCO-25-00809","url":null,"abstract":"<p><p>Approximately 30%-50% of patients develop acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation (Allo-HCT), representing a major limitation of this treatment. Although corticosteroids remain the standard first-line therapy for aGVHD, up to 50% of patients become steroid-refractory (SR). REACH2 is a phase III study of ruxolitinib versus best available therapy (BAT) in patients age 12 years and older with SR-aGVHD after Allo-HCT. We present the final efficacy and safety outcomes from REACH2 after 24 months of treatment. Cumulative median (range) duration of response was 167 (22-677) days with ruxolitinib and 106 (10-526) days with BAT. Median overall survival and event-free survival were 10.7 and 8.3 months for ruxolitinib, compared with 5.8 and 4.2 months, respectively, with BAT. Median failure-free survival was significantly longer with ruxolitinib than with BAT (4.86 <i>v</i> 1.02 months, <i>P</i> < .001). Similar numbers of nonrelapse mortality events were observed with ruxolitinib and BAT (72 <i>v</i> 71), and malignancy relapse/progression events remained low across both groups. Numerically higher chronic GVHD rates were noted with ruxolitinib than with BAT from 12 months; however, 95% confidence intervals overlapped. Safety observations were consistent with the primary analysis results. Ruxolitinib provided efficacy advantages over BAT in patients with SR-aGVHD over 24 months.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2500809"},"PeriodicalIF":41.9,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300903","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}