Randomized phase II study of sorafenib with or without low-dose IFN in patients with metastatic renal cell carcinoma

Abstract

5104 Background: An 80 patient randomized open label phase II study is underway evaluating the safety and clinical benefit of sorafenib with or without low-dose interferon (LD IFN) in patients with untreated metastatic conventional (clear cell) renal cell carcinoma (mRCC). Prior studies combining sorafenib and conventional dose IFN demonstrated a response rate (RR) in the 20–30 percent range, higher than the 2–10 percent RR seen with sorafenib monotherapy, but with increased toxicity. Prior data suggest equivalent efficacy between LD and conventional dose IFN with fewer side effects. We postulated that low-dose IFN will add to the clinical benefit of sorafenib in patients with mRCC with minimal additional toxicity. Methods: Eligibility included conventional mRCC, measurable disease, no prior systemic therapy, a PS of 0 or 1 and no brain metastases. Patients were treated with sorafenib 400mg PO BID or sorafenib at the same dose plus interferon alfa 0.5 million units SC BID. Primary endpoints included response rate and progression free survival (PFS). The probabilities of PFS and overall survival (OS) were estimated for each arm using Kaplan-Meier methods. Median PFS and OS were summarized, along with the 95% confidence intervals for each arm separately. Results: A total of 60 patients were enrolled as of January 8, 2007. Five patients were inevaluable, and 5 patients had not undergone first restaging. Treatment was well tolerated in both groups. Best response and PFS are summarized below. In the sorafenib arm, 13 out of 25 patients progressed or died. The median time to progression was 9.3 months (95% CI 5.8- not reached). In the sorafenib + IFN arm, 13 out of 25 patients progressed or died. Median time to progression was 9.3 months (95% CI 5.2- not reached). Median OS was not reached in either arm. Conclusions: These findings, although preliminary, suggest that adding low dose interferon therapy to sorafenib therapy does not provide superior cytoreduction of metastatic RCC, but provides equivalent PFS. [Table: see text] No significant financial relationships to disclose.