Medication Monitor

Generic Name (Trade Name—Company)
September 25, 2019

Lenvatinib and pembrolizumab

(Lenvima and Keytruda—Eisai, Merck Sharp & Dohme)
Drug combination approved for treatment of advanced endometrial carcinoma

FDA granted accelerated approval to lenvatinib in combination with pembrolizumab for treatment of patients with advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), and who have disease progression following prior systemic therapy but are not candidates for curative surgery or radiation.

The approval is part of Project Orbis, an initiative of FDA's Oncology Center of Excellence, in conjunction with decisions by Australian Therapeutic Goods Administration (TGA) and Health Canada. Project Orbis provides a framework for concurrent submission and review of oncology drugs among its international partners. Under this project, FDA, TGA, and Health Canada collaboratively reviewed applications for the two oncology drugs, allowing for simultaneous decisions in all three countries.

Lenvatinib was initially approved by FDA in 2015, and pembrolizumab was initially approved in 2014.

Approval of lenvatinib combined with pembrolizumab was based on the results of a clinical trial of 94 patients with endometrial carcinoma tumors that were not MSI-H or dMMR. Of the 94 patients, 10 patients (10.6% of responders) had a complete response, or disappearance of all lesions on imaging, and 26 patients (27.7% of responders) had a partial response, or shrinkage of lesions by at least 30%, leading to an objective response rate of 38.3%. Of these, 25 patients (69% of responders) have a duration of response of greater than 6 months. 

Common adverse effects included fatigue, high blood pressure, musculoskeletal pain, diarrhea, decreased appetite, hypothyroidism, nausea, and sore mouth.

Additional adverse effects included vomiting, decreased weight, abdominal pain, headache, constipation, urinary tract infection, dysphonia, hemorrhagic events, hypomagnesemia, palmar-plantar erythrodysesthesia, dyspnea, cough, and rash.

Health professionals should inform females of reproductive age and males with a female partner of reproductive potential to use effective contraception during treatment with the combination. Women who are pregnant or breastfeeding should not take this combination because it may cause harm to a developing fetus or newborn baby.