31: Updated efficacy of lenvatinib + pembrolizumab versus sunitinib in patients with advanced renal cell carcinoma (aRCC) in the CLEAR study

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Background: The phase 3 CLEAR study showed statistically significant PFS and OS benefits, and improved ORR with lenvatinib + pembrolizumab versus sunitinib in patients with aRCC in the 1L setting. We report updated efficacy and describe patients who completed 2 years of pembrolizumab and continued lenvatinib monotherapy.

Methods: Patients with aRCC and no prior systemic therapy were randomized (1:1:1) to receive lenvatinib 20 mg PO QD + pembrolizumab 200 mg IV Q3W; lenvatinib 18 mg + everolimus 5 mg PO QD; or sunitinib 50 mg PO QD (4 weeks on/2 weeks off). Randomization was stratified by geographic region and MSKCC prognostic group. In this descriptive follow-up analysis (data cutoff March 31, 2021), we report updated PFS, ORR, and DOR, by independent imaging review per RECIST v1.1 for lenvatinib + pembrolizumab and sunitinib, and an exploratory analysis of patients who completed 2 years of pembrolizumab and continued lenvatinib.

Results: The Table shows updated efficacy results. Median survival follow-up was 33.7 and 33.4 months for patients randomized to lenvatinib + pembrolizumab (N=355) and sunitinib (N=357), respectively. Of patients who completed 2 years of pembrolizumab (n=101), most (n=65) had IMDC intermediate/poor risk and fewer (n=36) had favorable risk disease, consistent with the intention-to-treat population. Pembrolizumab completers had a 36-month OS rate of 94.5%; 69 (68.3%) of these patients had treatment-related treatment-emergent adverse events.

Conclusions: Lenvatinib + pembrolizumab continued to show a clinically meaningful benefit versus sunitinib, consistent with prior results of the CLEAR study. A large proportion of patients treated with lenvatinib + pembrolizumab completed 2 years of pembrolizumab and continued with lenvatinib monotherapy with ongoing clinical benefit. The results further support lenvatinib + pembrolizumab as a standard of care in 1L aRCC.