Scientific Publications by FDA Staff

Clin Cancer Res 2015 Dec 1;21(23):5205-8

FDA approval summary: lenvatinib for progressive, radio-iodine-refractory differentiated thyroid cancer.

Nair A, Lemery SJ, Yang J, Marathe A, Zhao L, Zhao H, Jiang X, He K, Ladouceur G, Mitra AK, Zhou L, Fox E, Aungst S, Helms W, Keegan P, Pazdur R

The FDA approved LENVIMA (lenvatinib, Eisai Inc.) for the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory (RAI-refractory) differentiated thyroid cancer (DTC). In an international, multicenter, double blinded, placebo controlled trial (E7080-G000-303), 392 patients with locally recurrent or metastatic radioactive iodine-refractory differentiated thyroid cancer and radiographic evidence of disease progression within 12 months prior to randomization were randomly allocated (2:1) to receive either lenvatinib 24 mg orally per day (n = 261) or matching placebo (n = 131) with the option for patients on the placebo arm to receive lenvatinib following independent radiologic confirmation of disease progression. A statistically significant prolongation of progression-free survival (PFS) as determined by independent radiology review was demonstrated [HR 0.21 (95% CI: 0.16, 0.28); p < 0.001, stratified log-rank test], with an estimated median PFS of 18.3 months (95% CI: 15.1, NR) in the lenvatinib arm and 3.6 months (95% CI: 2.2, 3.7) in the placebo arm. The most common adverse reactions, in order of decreasing frequency, observed in the lenvatinib-treated patients were hypertension, fatigue, diarrhea, arthralgia/myalgia, decreased appetite, decreased weight, nausea, stomatitis, headache, vomiting, proteinuria, palmar-plantar erythrodysesthesia (PPE) syndrome, abdominal pain, and dysphonia. Adverse reactions led to dose reductions in 68% of patients receiving lenvatinib at the 24 mg dose and 18% of patients discontinued lenvatinib for adverse reactions leading to residual uncertainty regarding the optimal dose of lenvatinib.