Impact of subsequent therapies in patients (pts) with advanced renal cell carcinoma (aRCC) receiving lenvatinib plus pembrolizumab (LEN + PEMBRO) or sunitinib (SUN) in the CLEAR study.

Abstract

4514 Background: In the open-label, randomized, phase 3 CLEAR study, LEN + PEMBRO had significant PFS (primary endpoint) and OS (key secondary endpoint) benefits over SUN among pts with aRCC in the 1L setting (Motzer 2021, NEJM). We evaluated PFS on next-line therapy (“PFS2”) and explored the effect of subsequent anticancer therapy on OS in the LEN + PEMBRO and SUN treatment arms of CLEAR. Methods: PFS2 was defined as time from randomization to disease progression (as assessed by investigator) on next-line treatment or death from any cause (whichever occurred first). PFS2 was evaluated in all pts randomly assigned to LEN 20 mg orally QD + PEMBRO 200 mg IV Q3W (n=355) or SUN 50 mg orally QD (4 wks on/2 wks off) (n=357) using Kaplan-Meier estimates, and compared between treatment arms via a log-rank test stratified by geographic region and MSKCC prognostic groups. The HR and corresponding CI were estimated using the Cox regression model with Efron’s method for ties, using the same stratification factors. A post hoc analysis accounting for the effect of subsequent anticancer therapy on OS (time from randomization to death from any cause) in the LEN + PEMBRO and SUN arms using 2-stage estimation was conducted. Results: Among pts who received subsequent anticancer therapy in the LEN + PEMBRO (n=117 pts) and SUN (n=206 pts) arms (Table), median time to next-line therapy was 12.2 mos (range 1.45–37.36) and 6.4 mos (range 0.39–28.52), respectively. Median duration of first subsequent anticancer therapy was 5.2 mos (range 0.10–30.23) in the LEN + PEMBRO arm and 6.8 mos (range 0.03–30.72) in the SUN arm. Among all pts, PFS2 was longer with LEN + PEMBRO than with SUN (median not reached vs 28.7 mos; HR, 0.50; 95% CI 0.39–0.65; nominal P<0.0001); PFS2 rates at 24 and 36 mos are in the Table. The unadjusted OS HR for LEN + PEMBRO vs SUN (from the primary analysis [Motzer 2021, NEJM]) was 0.66 (95% CI 0.49–0.88); the HR for OS adjusted for subsequent therapy was 0.54 (bootstrap 95% CI 0.39–0.72). Conclusions: LEN + PEMBRO had a statistically significant and clinically meaningful benefit over SUN in the CLEAR study. These findings remained consistent after accounting for subsequent therapies, as evidenced by prolonged PFS2 and adjusted OS. Results further support LEN + PEMBRO as a standard of care in 1L aRCC. Clinical trial information: NCT02811861. [Table: see text]