Keytruda Monotherapy FDA Approved for Endometrial Carcinoma with a Biomarker

Web Exclusives - FDA Approvals

On March 21, 2022, the FDA approved a new indication for the PD-1 inhibitor pembrolizumab (Keytruda; Merck) as monotherapy for advanced endometrial carcinoma that is microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR), as determined by an FDA-approved test, in patients whose disease progressed after systemic therapy in any setting and who are not candidates for curative surgery or radiation therapy.

The FDA previously approved the combination of pembrolizumab plus lenvatinib (Lenvima) for patients with advanced endometrial carcinoma that is not MSI-H or dMMR.

On the same day, the FDA also approved the VENTANA MMR RxDx Panel (Ventana Medical Systems) as a companion diagnostic device for the selection of patients with solid tumors and dMMR who are eligible for pembrolizumab therapy. The FDA previously approved the FoundationOne CDx (F1CDx, by Foundation Medicine) as a companion diagnostic device for the selection of patients with solid tumors and MSI-H who are eligible for pembrolizumab therapy.

This approval was based on the KEYNOTE-158 clinical trial, a multicenter, nonrandomized, open-label, multicohort study of 90 patients with unresectable or metastatic MSI-H or dMMR endometrial carcinoma in cohorts D and K of the study. MSI-H or dMMR tumor status was determined using polymerase chain reaction and immunohistochemistry, respectively.

Patients received pembrolizumab 200 mg intravenously every 3 weeks until unacceptable toxicity or until disease progression. Patients without disease progression could continue to receive pembrolizumab for up to 24 months.

The major efficacy outcomes were objective response rate (ORR) and duration of response (DOR) using RECIST version 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The ORR was 46% (95% confidence interval, 35-56), and the median DOR was not reached; 68% of the patients had a response lasting ≥12 months, and 44% had a response lasting ≥24 months.

The most common (≥20%) adverse reactions in the study were fatigue, musculoskeletal pain, rash, diarrhea, pyrexia, cough, decreased appetite, pruritus, dyspnea, constipation, pain, abdominal pain, nausea, and hypothyroidism. The immune-mediated side effects associated with pembrolizumab include pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and skin reactions.

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Last modified: May 16, 2022
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