Phase 2 Trial of Capecitabine, Gemcitabine, and Bevacizumab in Sarcomatoid Renal-Cell Carcinoma.

BACKGROUND: Patients with sarcomatoid renal-cell carcinomas (sRCC) have poor outcomes and limited treatment options. Preclinical and clinical data suggest susceptibility to cytotoxic agents and vascular endothelial growth factor-targeted therapies. We designed a phase 2 trial to evaluate the efficacy and safety of capecitabine, gemcitabine, and bevacizumab in sRCC. PATIENTS AND METHODS: Patients with metastatic or unresectable sRCC were eligible for inclusion. Patients received oral capecitabine 800 mg/m2 twice daily on days 1 to 21 of a 28-day cycle, intravenous gemcitabine 900 mg/m2 on days 1 and 15, and intravenous bevacizumab 10 mg/kg on days 1 and 15. Primary end points were progression-free survival and time to treatment failure (TTF). Secondary end points were safety, objective response rate, and overall survival.
RESULTS: Thirty-four patients were enrolled onto the trial. One patient was excluded from survival analysis and 4 from response analysis as a result of missing data. Median progression-free survival was 5.5 months (95% confidence interval [CI], 3.4-7.7), median TTF was 4.2 months (95% CI, 2.4-6.0), and median overall survival was 12 months (95% CI, 10.6-13.4). Objective response rate was 20% (5 partial responses, 1 complete response), and disease control rate was 73%. Thirty-one (91%) of the 34 patients discontinued treatment. The most common reason for treatment discontinuation was progressive disease, which occurred in 24 patients (71%). The most common grade 3 toxicity was rash (including hand-foot syndrome) in 24% patients.
CONCLUSION: The combination of capecitabine, gemcitabine, and bevacizumab is an option for patients with sRCC; however, response rates are low. Novel therapies are needed to improve outcomes in patients with sRCC.