The U.S. Food and Drug Administration (FDA) has approved the kinase inhibitor lenvatinib, in combination with everolimus, for the treatment of patients with advanced renal cell carcinoma (RCC) who have received 1 prior anti-angiogenic therapy.1

The approval was based on findings from a multicenter study that randomly assigned 153 patients with advanced or metastatic RCC to receive lenvatinib plus everolimus, lenvatinib monotherapy, or everolimus monotherapy once daily. Metastases were present in 95% of patients, and 24%, 37%, and 39% of patients in the combination arm had a favorable, intermediate, and poor risk prognosis, respectively, according to the Memorial Sloan Kettering Cancer Center nomogram.

Results showed median progression-free survival was 14.6 months (95% CI, 5.9-20.1) with lenvatinib plus everolimus compared with 5.5 months (95% CI, 3.5-7.1) with everolimus alone (HR, 0.37; 95% CI, 0.22-0.62). Median overall survival was 25.5 months (95% CI, 16.4-32.1) and 15.4 months (95% CI, 11.8-20.6), respectively (HR, 0.67; 95% CI, 0.42-1.08). A total of 37% of patients in the combination arm achieved an objective response vs 6% with single-agent everolimus.

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In regard to safety, The most common adverse events with lenvatinib plus everolimus were diarrhea, fatigue, arthralgia/myalgia, decreased appetite, vomiting, nausea, stomatitis, hypertension, peripheral edema, cough, abdominal pain, dyspnea, rash, decreased weight, bleeding events, and proteinuria. The most frequently reported grade 3 to 4 adverse events were diarrhea, fatigue, hypertension, and renal failure event.

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The recommended dose and schedule is lenvatinib 18 mg orally once daily plus everolimus 5 mg orally once daily with or without food until disease progression or unacceptable toxicity.

Lenvatinib was initially approved in 2015 as a single-agent for the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer.                                       


  1. Lenvatinib in combination with everolimus. U.S. Food and Drug Administration website. May 13, 2016. Accessed May 16, 2016.