Final overall survival results from the phase II SWOG 1500 trial indicate that cabozantinib did not significantly improve overall survival compared to sunitinib in patients with advanced papillary renal cell carcinoma. The multicenter, open-label trial, initially designed to compare cabozantinib, sunitinib, crizotinib, and savolitinib, ultimately found no statistically significant difference in overall survival between the cabozantinib and sunitinib arms.
The trial enrolled 147 patients with advanced papillary renal cell carcinoma who had received up to one prior therapy, excluding VEGF-directed agents. Patients were randomized to receive sunitinib (n = 46), cabozantinib (n = 44), crizotinib (n = 28), or savolitinib (n = 29). The crizotinib and savolitinib arms were discontinued early due to futility. The primary analysis had previously demonstrated that cabozantinib significantly improved progression-free survival (9.0 vs 5.6 months) and objective response rate (23% vs 4%) compared to sunitinib.
Survival Analysis
With a median follow-up of 17.5 months, the median overall survival was 21.5 months (95% CI = 12.0–28.1 months) in the cabozantinib group and 17.3 months (95% CI = 12.8–21.8 months) in the sunitinib group. The hazard ratio for overall survival was 0.83 (95% CI = 0.51–1.36, P = .46). Overall survival rates at 24 and 36 months were 50% vs 39% and 32% vs 28% for cabozantinib and sunitinib, respectively. In the crizotinib and savolitinib arms, median overall survival was 19.9 months and 11.7 months, respectively.
Clinical Implications
The study's authors concluded that while cabozantinib is a reasonable option for advanced papillary renal cell carcinoma, the absence of a survival benefit highlights the necessity for developing new therapies for this disease. Sumanta K. Pal, MD, of the City of Hope Comprehensive Cancer Center, emphasized the need for continued research to address the unmet needs in this patient population.
Subsequent anticancer therapy was administered to 39% of patients in the cabozantinib group and 43% in the sunitinib group. This suggests that a significant proportion of patients required further treatment after initial therapy, underscoring the aggressiveness of advanced papillary renal cell carcinoma and the limitations of current treatment options.
