On August 10, 2021, the FDA accelerated the approval of the combination of lenvatinib (Lenvima; Eisai) and pembrolizumab (Keytruda; Merck) for the first-line treatment of adults with advanced renal-cell carcinoma (RCC). This combination received a breakthrough therapy designation for this indication.
This approval was based on the CLEAR study, a multicenter, open-label, randomized phase 3 clinical trial in patients with advanced RCC. The study included 355 patients who received lenvatinib plus pembrolizumab versus 357 who received single-agent sunitinib.
The primary end points were progression-free survival (PFS) and overall survival (OS). The median PFS was 23.9 months with the combination versus 9.2 months with sunitinib (P <.0001). The median OS was not reached in either arm. The objective response rate was 71% with the combination, including 16% complete responses, versus 36% (P <.0001) with sunitinib, including 4% complete responses.
Arterial thrombotic events occurred in 5% of patients in the CLEAR study, including myocardial infarction (3.4%) and cerebrovascular accident (2.3%).