Everolimus versus sunitinib prospective evaluation in metastatic non-clear cell renal cell carcinoma (The ESPN Trial): A multicenter randomized phase 2 trial.

Abstract

4505 Background: In a single-arm phase II trial of sunitinib in non-clear cell RCC (nccRCC) we previously reported (Tannir et al. Eur Urol 2012), objective response rate [ORR] was 5% and median progression-free survival [PFS] was 2.7 months. Temsirolimus was previously shown to produce overall survival (OS) benefit in poor-risk RCC including nccRCC (Hudes et al. NEJM 2007). Methods: This is a randomized phase II trial of everolimus (E) vs. sunitinib (S) with crossover design in metastatic nccRCC. Primary endpoint was PFS in first-line (1L). Secondary endpoints were PFS in second-line (2L), safety, and OS. A sample size calculation of 108 pts (54/arm) was based on an assumption of improved median PFS from 12 weeks with S to 20 weeks with E. Pts were stratified by histology (papillary vs. others), and MSKCC risk groups. Kaplan-Meier curves were used to estimate unadjusted time-to-event distributions. Stratified log rank tests were used to compare each time-to-event variable between groups. Results: Seventy-three pts were enrolled. Sixty-eight pts were eligible and evaluable (median age 59, 43 males [63%], 52 pts [77%] had prior nephrectomy). Twenty-seven pts had papillary, 11 pts had chromophobe, 9 pts had unclassified, 7 pts had translocation, 13 pts had sarcomatoid, and 1 pt had oncocytic RCC. Thirty-five pts received E (good-risk 4, intermediate-risk 29, poor-risk 2). Thirty-three pts received S (good-risk 4, intermediate-risk 29). ORR with S in 1L was 12% (2 pts had chromophobe, 1 pt had papillary type 1 and 1 pt had 99% sarcomatoid); ORR with E in 1L was 0%. Median PFS in 1L with S was 6.1 mos (95% CI: 4.7, 10.8) and 4.1 mos with E (95% CI: 2.7, 7.4); p = 0.25. Thirty-eight pts received 2L therapy (S 19, E 19). Median PFS in 2L with S was 1.8 mos (95% CI: 1.5, NA) and 4.3 mos with E (95% CI: 1.4, NA). A total of 27 pts have died (8 had S and 19 had E). Median OS with E in 1L was 10.5 mos (95% CI: 7.4, NA); median OS with S in 1L was not reached; p=0.01. Toxicity was consistent with previous reports of E and S. Conclusions: Based on futility analysis for PFS and inferior OS with E compared to S in 1L, the DSMB recommended termination of further pt accrual on this trial. E cannot be recommended as 1L option in nccRCC.