FDA Approves Pembrolizumab, Lenvatinib Combination Therapy for Advanced Endometrial Carcinoma


The FDA has approved pembrolizumab in combination with lenvatinib for the treatment of advanced endometrial carcinoma that is not microsatellite instability-high or mismatch repair deficient

The FDA has approved pembrolizumab (Keytruda, Merck) in combination with lenvatinib (Lenvima, Eisai) for the treatment of advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). Additionally, the combination therapy is specifically approved for patients who have experienced disease progression following prior systemic therapy in any setting, but who are not candidates for curative surgery or radiation.

After being granted accelerated approval for advanced endometrial carcinoma on September 17, 2019, the combination therapy was granted priority review and received breakthrough therapy designation for this indication. In the FDA’s review process, officials assessed data from the Study 309/KEYNOTE-775 trial to confirm the clinical benefit of an accelerated approval.

The Study 309/KEYNOTE-775 trial was multicenter, open-label, randomized, and active-controlled, with investigators enrolling 827 patients with advanced endometrial carcinoma who were previously treated with at least 1 prior platinum-based chemotherapy regimen in any setting, including neoadjuvant and adjuvant treatments.

During the study, patients were randomized 1 to 1 into a cohort administered pembrolizumab 200 mg intravenously every 3 weeks with lenvatinib 20 mg orally once daily or into a group administered the investigator’s choice of either doxorubicin or paclitaxel.

In the blinded independent central review’s (BICR’s) analysis of the study data, the major efficacy outcome measures were progression-free survival (PFS) and overall survival (OS). Additional efficacy outcome measures assessed by the BICR included the objective response rate (ORR) and duration of response (DOR).

The data compiled during the trial demonstrated that patients in the pembrolizumab and lenvatinib group with advanced endometrial cancer that is not MSI-H or dMMR had a median PFS of 6.6 months (95% CI: 5.6, 7.4), whereas patients given the investigator’s choice treatment had a PFS of 3.8 months (95% CI: 3.6, 5.0).

Additionally, the investigators observed that the median OS for patients in the pembrolizumab and lenvatinib group was 17.4 months (95% CI: 14.2, 19.9) and for the investigator’s choice treatment it was 12.0 months (95% CI: 10.8, 13.3). The investigators also found that the ORR was 30% (95% CI: 26, 36) and 15% (95% CI: 12, 19), with a median DOR of 9.2 months (1.6+, 23.7+) and 5.7 months (0.0+, 24.2+), respectively (p<0.0001).

For patients being treated with pembrolizumab in combination with lenvatinib, the most frequent adverse events reported in ≥ 20% of patients were hypothyroidism, hypertension, fatigue, diarrhea, musculoskeletal disorders, nausea, decreased appetite, vomiting, stomatitis, weight loss, abdominal pain, urinary tract infection, proteinuria, constipation, headache, hemorrhagic events, palmar-plantar erythrodysesthesia, dysphonia, and rash.

Based on the data and the findings of the study, the recommended dose of pembrolizumab for endometrial carcinoma is 200 mg every 3 weeks. However, with lenvatinib 20 mg orally once daily, the recommended dose of pembrolizumab is 400 mg every 6 weeks.


FDA. FDA grants regular approval to pembrolizumab and lenvatinib for advanced endometrial carcinoma. FDA website. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-regular-approval-pembrolizumab-and-lenvatinib-advanced-endometrial-carcinoma?utm_medium=email&utm_source=govdelivery. July 22, 2021. Accessed July 22, 2021.

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