On August 10, 2021, the FDA approved the combination of lenvatinib (Lenvima; Eisai) plus pembrolizumab (Keytruda; Merck) for the first-line treatment of adults with advanced renal-cell carcinoma (RCC). The FDA granted this combination a priority review and breakthrough therapy designation.
The FDA approved this combination based on the results of the multicenter, open-label, randomized, phase 3 CLEAR trial of patients with advanced RCC. The efficacy population supporting this approval included patients randomized to lenvatinib plus pembrolizumab (N = 355) compared with those randomized to sunitinib malate (Sutent; Pfizer) monotherapy (N = 357).
The primary end points of the study were progression-free survival (PFS) and overall survival (OS). Patients who received pembrolizumab with lenvatinib had a median PFS of 23.9 months compared with 9.2 months for those receiving sunitinib. Median OS was not reached in either arm of the study. The objective response rates were 71% and 36%; complete response rates were 16% and 4% on the combination and sunitinib arms, respectively.
The most common (≥ 20%) adverse reactions in patients receiving lenvatinib and pembrolizumab in clinical trials are fatigue, diarrhea, musculoskeletal pain, hypothyroidism, hypertension, stomatitis, decreased appetite, rash, nausea, decreased weight, dysphonia, proteinuria, palmar-plantar erythrodysesthesia syndrome, abdominal pain, hemorrhagic events, vomiting, constipation, hepatotoxicity, headache, and acute kidney injury. Arterial thrombotic events occurred in 5% of patients in the CLEAR trial, including myocardial infarction (3.4%) and cerebrovascular accident (2.3%).
