The CLEAR trial was an open-label phase 3 trial which demonstrated that lenvatinib + pembrolizumab had significant PFS and OS benefits over sunitinib as first-line therapy in advanced RCC. In this analysis, the authors 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.
In keeping with the protocol methodology, the authors defined PFS2 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. The authors compared outcomes between treatment arms via a log-rank test stratified by geographic region and MSKCC prognostic groups. The authors subsequently used Cox proportional hazards modeling with Efron’s method for ties, using the same stratification factors to calculate a hazard ratio (HR) with 95% CI. They further performed 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.
The authors found that, among all patients, PFS2 was longer among those randomized initially to lenvatinib + pembrolizumab than to sunitinib.
When stratified by risk group, as determined by either MSKCC or IMDC criteria, similar patterns were observed.
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).
In the primary analysis, the authors noted that the combination of lenvatinib + pembrolizumab had statistically significant and clinically meaningful benefits over sunitinib in CLEAR. In this updated analysis, this effect remained consistent after accounting for subsequent therapies, as evidenced by prolonged PFS2 and adjusted OS.
Presented by: Martin H. Voss, MD, Memorial Sloan Kettering Cancer Center, New York, NY