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FDA Approves Pembrolizumab–Lenvatinib Combo for Endometrial Carcinoma
The FDA granted accelerated approval to the combination of pembrolizumab (Keytruda, Merck) and lenvatinib (Lenvima, Eisai) for the treatment of advanced endometrial carcinoma that is not microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) and for patients whose disease progresses following prior systemic therapy but are not eligible for curative surgery or radiation.
The efficacy of this combination was demonstrated in Study111/KEYNOTE-146, which enrolled 108 patients with metastatic endometrial carcinoma that had progressed following ≥1 prior systemic therapy. Patients were treated with lenvatinib 20 mg orally once daily in combination with pembrolizumab 200 mg intravenously every 3 weeks until disease progression or unacceptable toxicity.
Of the 108 patients on the study, 94 had tumors that were not MSI-H or dMMR, 11 had tumors that were MSI-H or dMMR, and 3 patients had tumors where the MSI-H or dMMR status was not known.
The major efficacy outcome measures were objective response rate (ORR) and duration of response (DOR) by independent radiologic review committee using RECIST 1.1.
Among the 94 patients whose tumors were not MSI-H or dMMR, the ORR was 38.3% and included 10 (10.6%) complete responses and 26 (27.7%) partial responses. The median DOR was not reached at the time of data cutoff and 25 patients (69% of responders) had response durations ≥6 months.
The most common adverse events associated with lenvatinib and pembrolizumab (incidence ≥20%) 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.—Janelle Bradley
