FDA Grants Accelerated Approval of Pembrolizumab Plus Lenvatinib in Advanced Endometrial Carcinoma
Posted: Friday, September 20, 2019
On September 17, 2019, the U.S. Food and Drug Administration (FDA) granted accelerated approval to the combination of pembrolizumab (Keytruda) plus lenvatinib (Lenvima) for the treatment of patients with advanced endometrial carcinoma that is not microsatellite instability–high or mismatch repair–deficient and who have disease progression following prior systemic therapy but are not candidates for curative surgery or radiation therapy. The FDA, the Australian Therapeutic Goods Administration, and Health Canada collaborated on this review, allowing for simultaneous decisions in all three countries.
Efficacy was investigated in Study 111/KEYNOTE-146 (ClinicalTrials.gov identifier NCT02501096), a single-arm, multicenter, open-label, multicohort trial that enrolled 108 patients with metastatic endometrial carcinoma that had progressed after at least one prior systemic therapy in any setting. Patients were treated with lenvatinib at 20 mg orally once daily in combination with pembrolizumab at 200 mg administered intravenously every 3 weeks until unacceptable toxicity or disease progression. Among the 108 patients, 94 had tumors that were not microsatellite instability–high nor mismatch–repair deficient, 11 had tumors that were microsatellite instability–high or mismatch repair–deficient, and in 3 patients the status of tumor microsatellite instability–high or mismatch repair–deficient was not known.
The objective response rate in the 94 patients whose tumors were not microsatellite instability–high or mismatch repair–deficient was 38.3%, with 10 complete responses (10.6%) and 26 partial responses (27.7%). The median duration of response was not reached at the time of data cutoff, and 25 patients (69% of responders) had response durations of at least 6 months.
In endometrial carcinoma, the most common adverse reactions (incidence ≥ 20%) for lenvatinib and pembrolizumab were fatigue, hypertension, musculoskeletal pain, diarrhea, decreased appetite, hypothyroidism, nausea, stomatitis, vomiting, decreased weight, abdominal pain, headache, constipation, urinary tract infection, dysphonia, hemorrhagic events, hypomagnesemia, palmar-plantar erythrodysesthesia, dyspnea, cough, and rash.