Phase II study of sorafenib in patients with sunitinib-refractory metastatic renal cell cancer.

Purpose No previous prospective trials have been reported with sorafenib in patients with sunitinib-refractory metastatic renal cell cancer (MRCC). We conducted a multicenter study to determine the activity and tolerability of sorafenib as second-line therapy after sunitinib progression in MRCC. Patients and Methods Between January 2006 and September 2008, 52 patients were enrolled onto this single-arm phase II study. All patients received sorafenib 400 mg orally twice a day until disease progression or intolerable toxicity. The primary end point was objective response rate (complete or partial response) evaluated every 8 weeks by use of the Response Evaluation Criteria in Solid Tumors; secondary end points were toxicity, time to progression (TTP), and overall survival (OS). Results All patients were included in response and safety analyses. Partial responses were observed in 9.6% of patients (five of 52 patients; 95% CI, 5% to 17%) after two cycles. Grade 1 to 2 fatigue, diarrhea, nausea/vomiting, rash, and neutropenia were the most common side effects, noted in 16 (30.8%), 19 (36.5%), 20 (38.5%), 19 (36.5%), and 20 patients (38.5%), respectively. The most common grade 3 toxicity was diarrhea, noted in six patients (11.5%). Median TTP was 16 weeks (range, 8 to 40 weeks), and median OS was 32 weeks (range, 16 to 64 weeks). Conclusion Although well tolerated, sorafenib shows limited efficacy in sunitinib-refractory MRCC. Further randomized trials comparing sorafenib with other drugs that target different biologic pathways are needed to define the best second-line treatment option in these patients.