36: Impact of subsequent therapies in patients with advanced renal cell carcinoma (aRCC) receiving lenvatinib plus pembrolizumab or sunitinib in the CLEAR study

Width: Table .pdf

Background: In the open-label phase 3 CLEAR study, lenvatinib + pembrolizumab had significant PFS and OS benefits over sunitinib among patients with aRCC in the 1L setting. We evaluated PFS on next-line therapy (“PFS2”) and explored the effect of subsequent anticancer therapy on OS in the lenvatinib + pembrolizumab and sunitinib arms of CLEAR.

Methods: PFS2 was defined as time from randomization to disease progression (assessed by investigator) on next-line treatment or death from any cause (whichever occurred first). PFS2 was evaluated in all patients randomly assigned to lenvatinib 20mg orally QD + pembrolizumab 200mg IV Q3W (N=355) or sunitinib 50mg orally QD (4 weeks on/2 weeks 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 CI were estimated using Cox regression 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) using 2-stage estimation was conducted.

Results: Subsequent anticancer therapy is summarized in the Table. Among all patients, PFS2 was longer with lenvatinib + pembrolizumab than with sunitinib (Table). The unadjusted OS HR for lenvatinib + pembrolizumab versus sunitinib (from the primary analysis) 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: Lenvatinib + pembrolizumab had statistically significant and clinically meaningful benefits over sunitinib in CLEAR. Findings remained consistent after accounting for subsequent therapies, as evidenced by prolonged PFS2 and adjusted OS. Results further support lenvatinib + pembrolizumab as a standard of care in 1L aRCC.