Patients with advanced renal cell carcinoma with sarcomatoid features (sRCC) have poor prognoses and suboptimal outcomes with targeted therapy. This post hoc analysis of the phase III CheckMate 214 trial analyzed the efficacy of nivolumab plus ipilimumab (NIVO+IPI) versus sunitinib (SUN) in patients with sRCC.
Patients with sRCC were identified via independent central pathology review of archival tumor tissue or histological classification per local pathology report. Patients were randomized 1:1 to receive NIVO (3 mg/kg) plus IPI (1 mg/kg) Q3W (four doses) then NIVO 3 mg/kg Q2W, or SUN 50 mg orally QD (4 weeks; 6-week cycles). Outcomes in patients with sRCC were not prespecified. Endpoints in patients with sRCC and IMDC intermediate/poor-risk disease included overall survival (OS), progression-free survival (PFS) per independent radiology review, and objective response rate (ORR) per RECIST v1.1. Safety outcomes used descriptive statistics.
Of 1096 randomized patients in CheckMate 214, 139 patients with sRCC and intermediate/poor-risk disease and six with favorable-risk disease were identified. With 42 months' minimum follow-up in patients with sRCC and intermediate/poor-risk disease, median OS (95% CI) favored NIVO+IPI (NR [25.2-NE]; n=74) versus SUN (14.2 months [9.3-22.9]; n=65) (HR 0.45 [95% CI, 0.3-0.7; P=0.0004]); PFS benefits with NIVO+IPI were similarly observed (median 26.5 vs 5.1 months; HR 0.54 [95% CI, 0.33-0.86; P=0.0093]). Confirmed ORR was 60.8% with NIVO+IPI versus 23.1% with SUN, with complete response rates of 18.9% versus 3.1%, respectively. No new safety signals emerged.
NIVO+IPI showed unprecedented long-term survival, response and complete response benefits versus SUN in previously untreated patients with sRCC and intermediate/poor-risk disease, supporting the use of first-line NIVO+IPI for this population.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2020 Sep 01 [Epub ahead of print]
Nizar M Tannir, Sabina Signoretti, Toni K Choueiri, David F McDermott, Robert J Motzer, Abdallah Flaifel, Jean-Christophe Pignon, Miriam Ficial, Osvaldo Arén Frontera, Saby George, Frede Donskov, Michael R Harrison, Thomas Powles, Philippe Barthélémy, Scott S Tykodi, Judit Kocsis, Alain Ravaud, Jeronimo R Rodriguez-Cid, Sumanta K Pal, Andre M Murad, Yuko Ishii, Shruti Shally Saggi, M Brent McHenry, Brian I Rini
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center ., Department of Pathology, Brigham and Women's Hospital., Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School., Heme/Onc, Beth Israel Deaconess Medical Center, Harvard Medical School., Department of Medicine, Memorial Sloan Kettering Cancer Center., Pathology, Brigham and Women's Hospital., MEDICAL ONCOLOGY, CENTRO DE INVESTIGACION CLINICA BRADFORD HILL., Medicine, Roswell Park Cancer Institute., Department of Oncology, Aarhus University Hospital, Denmark., Divisions of Medical Oncology and Urology, Duke University, Duke Cancer Institute., Barts Cancer Institute, Queen Mary University of London, Royal Free NHS Trust., Medoical Oncology, Hôpitaux Universitaires de Strasbourg., Department of Medicine, University of Washington and Fred Hutchinson Cancer Research Center., Oncoradiology, Bács-Kiskun COunty Hospital., Medical Oncology, Hopital Saint-Andre, University Hospital., Centro Oncológico, Hospital Médica Sur., City Of Hope National Medical Center., Precision Oncology, CENANTRON-PERSONAL., Department of Clinical Trials, Bristol-Myers Squibb., Department of Clinical Trials, Bristol-Myers Squibb (United States)., Department of Biostatistics, Bristol-Myers Squibb (United States)., Cleveland Clinic Taussig Cancer Institute.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/32873572