Overall survival with sunitinib versus interferon (IFN)-alfa as first-line treatment of metastatic renal cell carcinoma (mRCC)

Abstract

5024 Background: In a randomized, phase III trial, sunitinib demonstrated statistically significant improvement in progression-free survival (PFS) and objective response rate (ORR) compared to IFN-alfa as first-line therapy in mRCC patients (pts) (P<0.001) [Motzer et al. NEJM 2007;356:115], establishing sunitinib as a new reference standard of care. At the time of last analysis, survival data were not mature. Median overall survival (OS) had not been reached in both treatment groups (HR=0.65; P=0.0219). Methods: Pts with mRCC were randomized 1:1 to receive sunitinib 50 mg orally once daily in 6-wk cycles (4 wks on treatment, 2 wks off) or IFN-alfa (9 MU subcutaneously thrice weekly). The primary endpoint was PFS. Secondary endpoints included ORR, safety and OS. For survival analysis, 390 events are required for a 2-sided, unstratified log-rank test with an overall 2-sided significance level of 0.05 and power of 0.85. Patients were followed for survival and post-study cancer treatment information was collected. The influence of baseline clinical features and previously identified prognostic factors on treatment effect will be analyzed with the use of a Cox proportional hazards model. Results: 750 pts were randomized to study treatment, 375 pts in each arm. Median duration of treatment was 11 mos (range: <1–39) for sunitinib vs 4 mos (range: <1–37) for IFN-alfa. 72 pts on sunitinib (including pts who crossed over from IFN-alfa) and 7 pts on IFN-alfa continue on the study. The updated ORR is 47% (95% CI: 42, 52) for sunitinib vs 12% (95% CI: 9, 16) for IFN-alfa (P<0.000001), including 11 complete responses for sunitinib and 4 for IFN-alfa. Median PFS remains the same as reported previously (11 mos vs 5 mos [P<0.000001]). The most common grade 3/4 treatment-related AEs for the sunitinib group are hypertension (12%), fatigue (11%), diarrhea and hand-foot syndrome (both 8%), and, for IFN-alfa, fatigue (13%) and anorexia (2%). No new unexpected grade 3/4 treatment-related AEs have been observed. Events are sufficient for final OS analysis. Conclusions: Sunitinib remains a reference standard for the first-line treatment of mRCC, with significantly superior efficacy over IFN-alfa. Final survival analysis will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Bayer, Genentech, Novartis, Pfizer, Wyeth Pfizer Bayer, Genentech, Novartis, Pfizer, Wyeth Bayer, Genentech, Pfizer, Wyeth