Randomized phase II multicenter study of the efficacy and safety of sunitinib on the 4/2 versus continuous dosing schedule as first-line therapy of metastatic renal cell carcinoma: Renal EFFECT Trial.

Abstract

LBA308 Background: In a randomized phase III trial, sunitinib 50 mg/d on Schedule 4/2 (4 wk on treatment [Tx], 2 wk off) showed superior progression-free survival (primary endpoint) to IFN-α (11 vs. 5 mo; p<0.001) as first-line metastatic renal cell carcinoma (mRCC) therapy with a median overall survival (OS) of >2 yr (Motzer 2009). Continuous dosing of sunitinib 37.5 mg has demonstrated antitumor activity with a manageable safety profile in first- and second-line mRCC (Barrios; Escudier, 2009). Methods: This randomized phase II trial compared sunitinib 50 mg/d on Schedule 4/2 (Arm A) vs. 37.5 mg continuous once-daily dosing (Arm B) in first-line mRCC. Eligible patients (pts) had clear cell locally recurrent or mRCC; measurable disease; and Karnofsky performance status ≥70%. Randomization (1:1) was stratified by MSKCC risk groups. Sunitinib was continued until progression, unacceptable toxicity, or up to 2 yr. The primary endpoint was time to tumor progression (TTP) by Kaplan-Meier estimate. Secondary endpoints included objective response rate (ORR), OS, and adverse events (AEs). Results: Between January 2007 and June 2008, 292 pts were randomized. As of October 2010, 289 pts had received sunitinib, and all pts were off therapy. Median age was 62 yr. 65% were male. By MSKCC criteria, 28%, 61%, and 11% were favorable, intermediate, and poor risk, respectively. Pts received a median 4 and 5 Tx cycles in Arms A and B, respectively; median relative dose intensity was 90.8% and 77.5%. Dose delays, reductions, and interruptions occurred in 30% vs. 13%, 36% vs. 43%, and 65% vs. 62%, respectively; 11% and 15% discontinued due to Tx-related AEs. Median TTP was 9.9 vs. 7.1 mo in Arms A and B, respectively (HR=0.773, 95.1% CI, 0.572, 1.044; p=0.090). ORR was 32.2% vs. 28.1% (p=0.444). Median OS was 23.1 vs. 23.5 mo (p=0.615). The most common Tx-related AEs were fatigue (both 62%), nausea (56% vs. 49%), and diarrhea (56% vs. 64%). Conclusions: In this randomized phase II mRCC trial, there was a trend toward inferior TTP with continuous dosing. ORR, OS, and AE profiles were similar for the approved sunitinib 50 mg/d dose on Schedule 4/2 vs. 37.5 mg continuous dosing. [Table: see text]