Eligible patients had untreated clear cell mRCC and Eastern Cooperative Oncology Group performance status of 0 to 2 and were intermediate or poor risk per International Metastatic Renal Cell Carcinoma Database Consortium criteria. Patients were randomly assigned at a one-to-one ratio to cabozantinib (60 mg once per day) or sunitinib (50 mg once per day; 4 weeks on, 2 weeks off). Progression-free survival (PFS) was the primary end point. Objective response rate (ORR), overall survival, and safety were secondary end points.
From July 2013 to April 2015, 157 patients were randomly assigned (cabozantinib, n = 79; sunitinib, n = 78). Compared with sunitinib, cabozantinib treatment significantly increased median PFS (8.2 v 5.6 months) and was associated with a 34% reduction in rate of progression or death (adjusted hazard ratio, 0.66; 95% CI, 0.46 to 0.95; one-sided P = .012). ORR was 46% (95% CI, 34 to 57) for cabozantinib versus 18% (95% CI, 10 to 28) for sunitinib. All-causality grade 3 or 4 adverse events were 67% for cabozantinib and 68% for sunitinib and included diarrhea (cabozantinib, 10% v sunitinib, 11%), fatigue (6% v 15%), hypertension (28% v 22%), palmar-plantar erythrodysesthesia (8% v 4%), and hematologic adverse events (3% v 22%).
Cabozantinib demonstrated a significant clinical benefit in PFS and ORR over standard-of-care sunitinib as first-line therapy in patients with intermediate- or poor-risk mRCC.
Toni K. Choueiri, Susan Halabi, Ben L. Sanford, Olwen Hahn, M. Dror Michaelson, Meghara K. Walsh, Darren R. Feldman, Thomas Olencki, Joel Picus, Eric J. Small, Shaker Dakhil, Daniel J. George, and Michael J. Morris
Toni K. Choueiri and Meghara K. Walsh, Dana-Farber Cancer Institute; M. Dror Michaelson, Massachusetts General Hospital Cancer Center, Boston, MA; Susan Halabi and Ben L. Sanford, Alliance Statistics and Data Center and Duke University; Daniel J. George, Duke Cancer Institute, Duke University Medical Center, Durham, NC; Olwen Hahn, Alliance Protocol Operations Office, Chicago, IL; Darren R. Feldman and Michael J. Morris, Memorial Sloan Kettering Cancer Center, New York, NY; Thomas Olencki, Ohio State University Medical Center, Columbus, OH; Joel Picus, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO; Eric J. Small, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA; and Shaker Dakhil, University of Kansas Wichita, Wichita, KS.
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