Journal of Clinical Oncology最新文献

{"title":"COMMIT: A Randomized Study of mFOLFOX6/Bevacizumab/Atezolizumab or Atezolizumab Alone as First-Line Treatment of Deficient DNA Mismatch Repair Metastatic Colorectal Cancer.","authors":"Caio Max Sao Pedro Rocha Lima, Greg Yothers, Thomas J George, Howard S Hochster, Hanna K Sanoff, Deirdre J Cohen, Katherine A Guthrie, Samuel A Jacobs, Anwaar Saeed, Scott Kopetz, Linda H Colangelo, Tanner J Freeman, Scott W Cole, Maged Khalil, Swapna Devanna, Dan S Zuckerman, Theodore S Hong, N Lynn Henry, Patricia A Ganz, Charles D Blanke, Norman Wolmark, Michael J Overman","doi":"10.1200/JCO-25-03052","DOIUrl":"10.1200/JCO-25-03052","url":null,"abstract":"<p><strong>Purpose: </strong>Immunotherapy for frontline mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer (mCRC) is effective; however, nearly half of the patients treated with single-agent PD-1 therapy will progress within 12 months. Preclinical studies in CRC and clinical data from other cancers suggest that vascular endothelial growth factor inhibition and chemotherapy can synergize with PD-L1 inhibition.</p><p><strong>Methods: </strong>The NRG-GI004/SWOG-S1610 (COMMIT) three-arm prospective phase III open-label trial randomly assigned first-line dMMR/MSI-H mCRC patients (1:1:1) to either: mFOLFOX6 (oxaliplatin 85 mg/m², leucovorin 400 mg/m², 5-FU bolus 400 mg/m², and 46-hour infusional 5-FU 2,400 mg/m²)/bevacizumab (FFX/bev), or atezolizumab (atezo) monotherapy (840 mg IV once every 2 weeks), or the combination of FFX/bev/atezo. The primary end point was progression-free survival (PFS) in the intent-to-treat population. Because of KEYNOTE 177 results, the FFX/bev arm was closed after 20 patients were enrolled. The study continued with atezo alone versus FFX/bev/atezo, with a revised sample size of 100 patients in the two remaining arms (120 patients across all three arms).</p><p><strong>Results: </strong>From November 2017 to March 2025, a total of 102 patients were enrolled in the three arms: FFX/bev: n = 20, atezo: n = 41, and FFX/bev/atezo: n = 41. At a median follow-up of 46 months for the two arms (median age: 63.3 years; 47.6% female; 23.2% <i>BRAF V600E</i> mutated), PFS of FFX/bev/atezo was superior to that of atezo (hazard ratio [HR], 0.439 [95% CI, 0.23 to 0.84]; <i>P</i> = .0103) and below the critical value of 0.0152. The objective response rate was 86.1% versus 46%, and the disease control rate at 12 months was 64.7% versus 32.4% in the FFX/bev/atezo arm compared with the atezo-only arm, respectively. Grade 3 or higher adverse events of any attribution occurred in 52 patients (atezo: 18; combination arm: 34).</p><p><strong>Conclusion: </strong>The combination of FFX/bev plus atezo led to significantly longer PFS compared with atezo monotherapy in the first-line treatment of dMMR/MSI-H mCRC.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2824-2834"},"PeriodicalIF":44.7,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13459625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620211","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":"High-Risk Smoldering Multiple Myeloma: A Review of Controversies in Early Treatment Versus Observation.","authors":"María-Victoria Mateos, Joshua Gustine, Borja Puertas, Noopur Raje","doi":"10.1200/JCO-26-00236","DOIUrl":"10.1200/JCO-26-00236","url":null,"abstract":"<p><p>Smoldering multiple myeloma (SMM) is an asymptomatic but biologically heterogeneous plasma cell disorder with a variable risk of progression to multiple myeloma (MM). Accurate risk stratification is essential as only a subset of patients-defined as high-risk SMM -faces a ≥50% risk of progression within 2 years. Contemporary approaches integrating clinical variables, dynamic biomarkers, genomic alterations, and immune profiling have improved risk assessment although some limitations remain. The therapeutic paradigm of SMM is evolving. Randomized phase III trials have consistently shown that early treatment delays progression to MM. Most recently, daratumumab monotherapy became the first approved treatment for high-risk-SMM following the AQUILA trial, which demonstrated a significant progression-free survival benefit (hazard ratio [HR], 0.49 [95% CI, 0.36 to 0.67], <i>P</i> < .001) and a trend toward improved overall survival (OS; HR, 0.52 [95% CI, 0.27 to 0.98]) versus observation. This approval challenges the traditional watch-and-wait approach and establishes early intervention as a validated option for selected patients. However, important uncertainties persist. With modern surveillance and advanced imaging, most progression events are asymptomatic and irreversible end-organ damage is uncommon. OS benefit from early treatment remains inconclusive, particularly in the era of quadruplet regimens available at MM progression. In addition, difficulties in precisely identifying truly high-risk patients raise concerns about overtreatment. Emerging data from intensive regimens, bispecific antibodies, and chimeric antigen receptor -T cell therapies suggest that deep and durable responses-and possibly cure-may be achievable in selected patients with high-risk-SMM, but long-term benefit and safety require further study. In conclusion, following the approval of daratumumab, SMM management should be risk-adapted and patient-centered: observation remains appropriate for some patients, while early treatment should be considered for carefully selected high- and ultrahigh-risk individuals.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2865-2874"},"PeriodicalIF":44.7,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148630396","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: Five-Year Clinical Outcomes With Nivolumab Plus Ipilimumab Versus Chemotherapy as First-Line Treatment for Unresectable Pleural Mesothelioma in CheckMate 743.","authors":"Arnaud Scherpereel, Paul Baas, Anna K Nowak, Anne S Tsao, Nobukazu Fujimoto, Solange Peters, Aaron S Mansfield, Sanjay Popat, Yolanda Bautista Aragon, Toby Talbot, Francesco Grossi, Dariusz Kowalski, Muhammet A Kaplan, Andrés Felipe Cardona, Raheela Soomro, Nan Hu, Adam Lee, Virginia Ip, Yu-Han Hung, Gérard Zalcman","doi":"10.1200/JCO-26-02181","DOIUrl":"10.1200/JCO-26-02181","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2878"},"PeriodicalIF":44.7,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148919880","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 Inclusion of Representative Populations in Pivotal Clinical Trials: Zolbetuximab as an Example.","authors":"Youngwoo Cho, Axel-R Hanauske, Mark J Ratain","doi":"10.1200/JCO-26-01002","DOIUrl":"10.1200/JCO-26-01002","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2773-2776"},"PeriodicalIF":44.7,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13528863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148678848","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":"Reply to: When <i>PIK3CA</i> Wild-Type Becomes a Biomarker Blind Spot.","authors":"Sara A Hurvitz, Rachel M Layman, Giuseppe Curigliano, Barbara Pistilli","doi":"10.1200/JCO-26-01653","DOIUrl":"https://doi.org/10.1200/JCO-26-01653","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2601653"},"PeriodicalIF":44.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148179","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":"When <i>PIK3CA</i> Wild-Type Becomes a Biomarker Blind Spot.","authors":"Dongli Zhao, Rui Liu, Yiping Qu, Jian Zhang, Yongkai Lu","doi":"10.1200/JCO-26-00661","DOIUrl":"https://doi.org/10.1200/JCO-26-00661","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2600661"},"PeriodicalIF":44.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149557","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":"Phase I/II Study of Bavdegalutamide, a Proteolysis-Targeting Chimera Androgen Receptor Degrader, in Metastatic Castration-Resistant Prostate Cancer.","authors":"Xin Gao, Benjamin Garmezy, Jacqueline Vuky, John Shen, Oliver Sartor, Cora N Sternberg, Robert Dreicer, Maha Hussain, Arash Rezazadeh Kalebasty, Ivor J Percent, Elisabeth I Heath, Sunil Gandhi, Benjamin L Maughan, Xin Zhi, Sean Landrette, Jiachang Gong, Diane Healey, Janaki Parameswaran, Daniel P Petrylak","doi":"10.1200/JCO-25-02995","DOIUrl":"https://doi.org/10.1200/JCO-25-02995","url":null,"abstract":"<p><strong>Purpose: </strong>This phase I/II study (which, to our knowledge, is the first such study in humans) evaluated the safety and efficacy of bavdegalutamide (ARV-110), a proteolysis-targeting chimera (PROTAC) androgen receptor (AR) degrader, in patients with metastatic castration-resistant prostate cancer (mCRPC).</p><p><strong>Patients and methods: </strong>Eligible patients were adult (18 years and older) males with mCRPC previously treated with an AR pathway inhibitor (ARPI). In phase I, patients received escalating doses of oral bavdegalutamide to determine the recommended phase II dose (RP2D). In phase II, patients received bavdegalutamide at the RP2D in 28-day cycles. Antitumor activity, including prostate-specific antigen (PSA) response rate (≥50% [PSA₅₀] or ≥30% [PSA₃₀] decline from baseline) and radiographic progression-free survival (rPFS), was assessed in three AR molecular profile-defined subgroups and a less-pretreated (one prior ARPI without prior chemotherapy) subgroup.</p><p><strong>Results: </strong>In phase I (N = 95), bavdegalutamide 420 mg once daily was the RP2D. In phase II, PSA₅₀ and PSA₃₀ rates, respectively, were 60.0% and 70.0% among patients with tumors harboring <i>AR</i> T878 and/or H875 mutations (n = 20), 4.3% and 6.5% among those with wild-type <i>AR</i> or other <i>AR</i> alterations (n = 46), and 3.1% and 6.3% among those with <i>AR</i> L702H mutations or AR splice variant 7 expression (n = 32); the median rPFS was 11.1, 4.2, and 5.1 months in the respective subgroups. Among less-pretreated patients (n = 42), the PSA₅₀ rate was 21.4%, the PSA₃₀ rate was 23.8%, and the median rPFS was 11.1 months. Among phase II patients (n = 144), 72.3% experienced grade 1/2 treatment-related adverse events (TRAEs) and 17.4% experienced grade 3 TRAEs; no grade ≥4 TRAEs occurred. TRAEs led to dose reduction and discontinuation in 11.8% and 11.1% of patients, respectively.</p><p><strong>Conclusion: </strong>Bavdegalutamide had a manageable safety profile and showed promising clinical activity in patients with mCRPC, particularly those with tumors harboring <i>AR</i> T878/H875 mutations.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2502995"},"PeriodicalIF":44.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147831","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":"Disentangling Resection From Treatment Response in SAKK 06/19.","authors":"Francesco Claps, Roberto Contieri, Benjamin Pradere, Laura S Mertens","doi":"10.1200/JCO-26-01949","DOIUrl":"https://doi.org/10.1200/JCO-26-01949","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2601949"},"PeriodicalIF":44.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136811","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":"Prognostic Impact of Telomere Maintenance Mechanisms in Neuroblastoma.","authors":"Carolina Rosswog, Magdalena Sol Grauer, Fynn Goossens, Andreas Kuckelkorn, Christoph Bartenhagen, Nadine Hemstedt, Yvonne Kahlert, Judith Gecht, Wibke Schumacher, Sophia Gunzer, Jessica Theissen, Lisa Werr, Óscar González-Velasco, Sadaf Shabbir Mughal, Roman Kurilov, Sandra Ackermann, René Schmidt, Benedikt Brors, Frank Berthold, Martin Peifer, Thorsten Simon, Barbara Hero, Matthias Fischer","doi":"10.1200/JCO-26-00742","DOIUrl":"https://doi.org/10.1200/JCO-26-00742","url":null,"abstract":"<p><strong>Purpose: </strong>Neuroblastoma, a common cancer in children, is characterized by striking clinical heterogeneity, ranging from spontaneous regression to fatal disease. Precise risk classification is therefore essential for appropriate treatment stratification. Given that genotoxic chemotherapy constitutes the mainstay of neuroblastoma treatment, it is particularly important to avoid overtreatment in patients with biologically favorable disease, notably in the heterogeneous group of current non-high-risk patients. Here, we tested the hypothesis that telomere maintenance mechanisms (TMM), which have been proposed as key hallmark of high-risk neuroblastoma, may improve neuroblastoma risk classification over current standard of care.</p><p><strong>Methods: </strong>We examined the prognostic accuracy of TMM in comparison with current standard-of-care prognostic variables in 366 patients with neuroblastoma, including 259 non-high-risk patients (test set, n = 116; validation set, n = 143). Patient event-free survival (EFS) and overall survival (OS) were determined according to TMM and currently used molecular classification by chromosomal copy-number alterations or gene expression profiles. The prognostic impact of the three molecular classifications was compared pairwise and with standard-of-care prognostic variables in multivariable analyses.</p><p><strong>Results: </strong>TMM-based and gene expression-based classification accurately distinguished non-high-risk patients with excellent and adverse EFS and OS in both the test and validation sets. On multivariable analyses of standard-of-care prognostic factors, TMM-based classification remained the only risk factor in the final models (EFS, hazard ratio [HR], 6.4 [95% CI, 3.9 to 10.6], <i>P</i> < .001; OS, HR, 29.4 [95% CI, 9.6 to 90.0], <i>P</i> < .001), in contrast to the two other molecular classifiers. In pairwise comparisons, TMM-based classification outperformed the two other molecular classifications in models built on both EFS and OS (<i>P</i> < .001 each).</p><p><strong>Conclusion: </strong>TMM-based classification improves risk assessment in neuroblastoma, providing a rationale for clinical implementation as a new standard for risk stratification of patients with neuroblastoma.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2600742"},"PeriodicalIF":44.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136817","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 Melanoma's Differentiation State to Settle the Combination Versus Sequencing Debate.","authors":"Drew Hurd, Diwakar Davar","doi":"10.1200/JCO-26-01593","DOIUrl":"https://doi.org/10.1200/JCO-26-01593","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2601593"},"PeriodicalIF":44.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136823","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}