FDA Approves Pembrolizumab in MSI H/dMMR Advanced Endometrial Carcinoma


The FDA has approved pembrolizumab to treat patients with endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient, as determined by an FDA-approved test.

The FDA has approved pembrolizumab (Keytruda) as a monotherapy to treat patients with microsatellite instability–high (MSI-H) or mismatch repair deficient (dMMR) advanced endometrial carcinoma.1 Under the indication, patients must have experienced disease progression following prior systematic therapy in any setting and must not be candidates for curative surgery or radiation in order to be eligible for the PD-1 inhibitor.

This approval is supported by findings from cohorts D and K of the KEYNOTE-158 trial (NCT02628067). Findings showed that the objective response rate (ORR) was 46% (95% CI, 35%-56%) among patients who received pembrolizumab. Furthermore, at a median follow-up time of 16.0 months (range, 0.5-62.1 months), the complete response (CR) rate among this population was 12% and the partial response rate was 33%.

Among patients who responded to treatment, 68% reported responses lasting 12 months or longer, and 44% reported responses lasting 24 months or longer. No median duration of response (DOR) was reached (range, 2.9-55.7 months).

"New data from the KEYNOTE-158 trial showed an objective response rate of 46% for certain patients with advanced endometrial carcinoma that is MSI-H or dMMR treated with Keytruda," David O’Malley, MD, of the Division of Gynecologic Oncology, The Ohio State University Wexner Medical Center and The James Comprehensive Cancer Center, said in a news release. "The objective response rate and duration of response observed in this trial solidify the role of Keytruda as a treatment option for these patients."

KEYNOTE-158 is a multicenter, non-randomized, open-label, multi-cohort trial designed to assess the efficacy of pembrolizumab among patients with unresectable or metastatic MSI-H or dMMR endometrial carcinoma. If patients had an autoimmune disease or required an immunosuppressing medicine, they were ineligible to enroll. The trial used polymerase chain reaction or immunohistochemistry to determine MSI-H or MMR tumor status.

Patients received intravenous pembrolizumab at a dose of 200 mg every 3 weeks until unacceptable toxicity or disease progression occurred. Treatment could continue up to 24 months so long as there was no disease progression. ORR and DOR represented the primary trial objectives.

Common adverse events observed in patients receiving pembrolizumab include hypertension, cardiac dysfunction, arterial thromboembolic events, hepatotoxicity, renal failure or impairment, proteinuria, diarrhea, fistula formation and gastrointestinal perforation, QT interval prolongation, hypocalcemia, reversible posterior leukoencephalopathy syndrome, hemorrhagic events, impairment of thyroid stimulating hormone suppression/thyroid dysfunction, impaired wound healing, osteonecrosis of the jaw, and embryo-fetal toxicity.

Because pembrolizumab is an immunotherapy, immune-related AEs can occur. In these cases, it may be appropriate to withhold or discontinue pembrolizumab, and to administer corticosteroids to the patient.1

"This FDA approval is great news for women facing advanced endometrial cancer," Scot Ebbinghaus, MD, vice president, clinical research, Merck Research Laboratories, said in the press release. "We have seen substantial progress in delivering treatment options for patients with advanced endometrial cancer with Keytruda, as monotherapy and in combination, with two approved indications in this area. We remain committed to pursuing meaningful advances in gynecologic and breast cancers through our portfolio of medicines."

This approval marks pembrolizumab’s second FDA approval for endometrial carcinoma. The agent is also approved in combination with lenvatinib (Lenvima) to treat patients with advanced endometrial carcinoma that is not MSI-H or dMMR and whose disease has progressed following prior systematic treatment, but who are not eligible for surgery.


  • FDA approves Merck’s KEYTRUDA® (pembrolizumab) for patients with MSI‑H/dMMR advanced endometrial carcinoma, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation. Business Wire. News release. March 21, 2022. Accessed March 21, 2022. https://yhoo.it/3tqQ5IQ

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