A randomized phase II clinical trial evaluating cabozantinib (Cabometyx) compared with standard-of-care sunitinib (Sutent) as first-line therapy for patients with advanced renal cell carcinoma has found that cabozantinib reduced the rate of disease progression or death by 34% compared with sunitinib. In addition, the overall response rate of cabozantinib was superior over sunitinib, with 46% of patients achieving a complete or partial response vs 18% in the sunitinib group. The safety and side effects of the drugs were similar.

Cabozantinib, an oral small-molecule inhibitor of tyrosine kinases, including vascular endothelial growth factor receptors (VEGFRs), MET, and AXL, may provide a potential new treatment option for patients with previously untreated metastatic renal cell carcinoma. This study by Choueiri et al was published in the Journal of Clinical Oncology. ¹

Study Methodology

The clinical trial included 157 patients, 18 years or older, with advanced renal cell carcinoma or metastatic renal cell carcinoma, not amenable to curative surgery or radiotherapy, with a clear cell component and measurable disease. The patients were enrolled in the study from July 2013 to April 2015 and classified as intermediate or poor risk by International Metastatic Renal Cell Carcinoma Database Consortium criteria; they must not have received prior systemic treatment. Eligible patients also had to have an Eastern Cooperative Oncology Group performance status of 0 to 2 and adequate end-organ and marrow function, with no uncontrolled significant illness.

Trial participants were randomly assigned to receive cabozantinib (79 patients; 60 mg once per day) or sunitinib (78 patients; 50 mg once per day; 4 weeks on, 2 weeks off). Progression-free survival was the primary endpoint. Objective response rate, overall survival, and safety were secondary endpoints.

Study Results

Compared with sunitinib, cabozantinib treatment significantly increased median progression-free survival (8.2 vs 5.6 months) and was associated with a 34% reduction in the rate of disease progression or death (adjusted hazard ratio = 0.66; 95% confidence interval [CI] = 0.46–0.95; one-sided P = .012). Objective response rate was 46% (95% CI = 34%–57%) for cabozantinib vs 18% (95% CI = 10%–28%) for sunitinib. All-causality grade 3 or 4 adverse events were 67% for cabozantinib and 68% for sunitinib and included diarrhea (cabozantinib, 10% vs sunitinib, 11%), fatigue (6% vs 15%), hypertension (28% vs 22%), palmar-plantar erythrodysesthesia (8% vs 4%), and hematologic adverse events (3% vs 22%).

“These results are very relevant to our practice and our kidney cancer patients—they may change the standard,” said Toni K. Choueiri, MD, Director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute and lead author of this study, in a statement. “The results also demonstrate that studies sponsored by the National Cancer Institute can accrue rapidly and yield highly relevant results to the field.” 

Disclosure: The study was funded by the National Institutes of Health. For full disclosures of the study authors, visit www.jco.org. ■

Reference

1. Choueiri TK, Halabi S, Sanford BL, et al: Cabozantinib versus sunitinib as initial targeted therapy for patients with metastatic renal cell carcinoma of poor or intermediate risk: The Alliance A031203 CABOSUN Study. J Clin Oncol. November 14, 2016 (early release online).