Adjuvant Nivolumab in High-Risk Muscle-Invasive Urothelial Carcinoma: Expanded Efficacy From CheckMate 274
Abstract
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported . CheckMate 274 is a phase III, randomized, double-blind trial of adjuvant nivolumab versus placebo for muscle-invasive urothelial carcinoma (MIUC) at high risk of recurrence after radical resection. The primary end points of disease-free survival (DFS) in intent-to-treat (ITT) and tumor PD-L1 expression ≥1% populations were met. We report results at an extended median follow-up of 36.1 months in the ITT population. In addition, we report interim overall survival (OS) data for the first time and an exploratory analysis among patients with bladder primary tumors (muscle-invasive bladder cancer [MIBC]). Consistent DFS benefit with nivolumab versus placebo was observed in both the ITT (hazard ratio [HR], 0.71 [95% CI, 0.58 to 0.86]) and PD-L1 ≥1% (HR, 0.52 [95% CI, 0.37 to 0.72]) patients. The HR for OS with nivolumab versus placebo was 0.76 (95% CI, 0.61 to 0.96) in the ITT population and 0.56 (95% CI, 0.36 to 0.86) in the PD-L1 ≥1 population. Continuous benefit in nonurothelial tract recurrence-free survival and distant metastasis-free survival was also observed in both patient populations. The exploratory analysis of patients with MIBC also showed continued efficacy benefits, irrespective of PD-L1 status. No new safety signals were reported. Overall, these results further support adjuvant nivolumab as a standard of care for high-risk MIUC after radical resection.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (22)
Matthew D. Galsky
Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai
Johannes Alfred Witjes
Department of Urology, Radboud University, Nijmegen, Netherlands
Jürgen E. Gschwend
Technical University Munich, Munich, Germany
Matthew I. Milowsky
Michael Schenker
Department of Oncology, University of Medicine and Pharmacy of Craiova, Craiova, Romania
Begoña P. Valderrama
Hospital Universitario Virgen del Rocío, Seville, Spain
Yoshihiko Tomita
Department of Urology, Niigata University Graduate School of Medicine and Dental, Niigata-Shi, Japan
Aristotelis Bamias
Second Propaedeutic Department of Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, Athens
Thierry Lebret
Department of Urology, Suresnes, France
Shahrokh F. Shariat
Se Hoon Park
Mads Agerbaek
Aarhus University Hospital, Aarhus, Denmark
Gautam Jha
M Health Fairview Clinics and Surgery Center, Minneapolis, MN
Frank Stenner
Department of Oncology, University Hospital Basel, Basel, Switzerland
Dingwei Ye
Fudan University Shanghai Cancer Center, Shanghai
Fabio Giudici
Bristol Myers Squibb, Boudry, Switzerland
Santanu Dutta
Bristol Myers Squibb, Princeton, NJ
Margarita Askelson
From the Sandra and Edward Meyer Cancer Center (J.D.W.) and the Department of Medicine (J.D.W., M.A.P.), Weill Cornell Medicine, and Memorial Sloan Kettering Cancer Center (M.A.P.) — both in New York; Istituto Oncologico Veneto, IRCCS, Padua (V.C.-S.), European Institute of Oncology, IRCCS, Milan (P.Q.), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, IRCCS, Meldola (M.G.), University of Siena and the Center for Immuno-Oncology, University Hospital of Siena, Siena (M.M.), and Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples (P.A.A.) — all in Italy; Maria Sklodowska-Curie National Institute of Oncology, Warsaw, Poland (P.R.); Texas Oncology–Baylor Charles A. Sammons Cancer Center, Dallas (C.L.C.); University Hospital Essen, the German Cancer Consortium, the National Center for Tumor Diseases–West, the Research Alliance Ruhr, Research Center One Health, and University Duisburg-Essen — all in Essen, Germany (D.S.); the College of Medicine, Swansea University, Swansea (J.W.), Brist...
Federico Nasroulah
Bristol Myers Squibb, Princeton, NJ
Joshua Zhang
UCLA
Lynne Brophy
Bristol Myers Squibb, Princeton, NJ
Dean F. Bajorin
Memorial Sloan Kettering Cancer Center, New York, NY