FDA Approves Pembrolizumab for MSI‑H/dMMR Advanced Endometrial Carcinoma


Pembrolizumab (Keytruda) approved as a single agent for the treatment of patients with microsatellite instability–high or mismatch repair deficient advanced endometrial carcinoma.

The FDA has approved pembrolizumab (Keytruda) as a single agent for the treatment of patients with microsatellite instability–high (MSI-H) or mismatch repair deficient (dMMR) advanced endometrial carcinoma, and who experienced disease progression after prior systemic therapy in any setting and who are not candidates for curative surgery or radiation.1

The approval was based on findings from cohorts D and K of the phase 2 KEYNOTE-158 trial (NCT02628067). At a median follow-up of 16.0 months (range, 0.5-62.1), pembrolizumab produced an objective response rate of 46% (95% CI, 35%-56%), with a complete response (CR) rate of 12% and a partial response (PR) rate of 33%.

Among the 41 patients who responded, 68% experienced responses that lasted for 12 months or longer, and 44% had responses that lasted for 24 months or longer. Further, the median duration of response (DOR) with pembrolizumab in these responders had not yet been reached (range, 2.9-55.7+).

“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 [pembrolizumab],” David M. O’Malley, MD, of the Division of Gynecologic Oncology at The Ohio State University Wexner Medical Center and The James Comprehensive Cancer Center, said in a press 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 was a multicenter, non-randomized, open-label, multi-cohort trial that included 90 patients with unresectable or metastatic MSI-H or dMMR endometrial carcinoma who received at least 1 dose of pembrolizumab. Microsatellite instability-high or MMR tumor status was determined using polymerase chain reaction or immunohistochemistry, respectively. Patients with autoimmune disease or a medical condition that required immunosuppression were ineligible.

Patients were administered pembrolizumab 200 mg intravenously every 3 weeks until unacceptable toxicity or documented disease progression. Those treated with pembrolizumab without disease progression could be treated for up to 24 months.

An assessment of tumor status was conducted every 9 weeks for the first 12 months, and every 12 weeks thereafter. The major efficacy outcome measures were ORR and DOR as assessed by blinded independent central review according to RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.

Among the 90 patients with MSI-H or dMMR endometrial carcinoma enrolled in KEYNOTE-158 administered pembrolizumab as a single agent, the median duration of exposure to pembrolizumab was 8.3 months (range, 1 day to 26.9 months). Adverse events (AEs) in patients with endometrial carcinoma were found to be similar to those recorded in 2799 patients with melanoma or non-small cell lung cancer treated with pembrolizumab as a single agent.

The showed that pembrolizumab produced an ORR of 48% (95% CI, 37%-60%) per independent central radiologic (ICR) review in 79 patients who comprised the efficacy analysis population. Of the patients who responded, 14% achieved a CR and 34% experienced a PR.

Further, 21 of the 38 patients who achieved a CR, including 8 of 11 with confirmed CR, had ongoing responses at the time of data cutoff, which was October 5, 2020. Eighteen percent of patients had stable disease, and 13 of those 14 patients showed a decreased tumor size from baseline.

Median PFS with pembrolizumab was 13.1 months (95% CI, 4.3-34.4). The estimated 1- and 2-year PFS rates were 51% and 41%, respectively; at 3 and 4 years, this rate was 37%. Moreover, the median OS was not reached in these patients. The Kaplan-Meier estimated 1-year, 2-year, and 3- and 4-year OS rates were 69%, 64%, and 60%, respectively. Fifty-seven percent of patients experienced disease progression or died.

Immune-mediated AEs reported with pembrolizumab include pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, and complications associated with allogeneic hematopoietic stem cell transplantation.

“This FDA approval is great news for women facing advanced endometrial cancer,” Scot W. Ebbinghaus, MD, vice president of clinical research at Merck Research Laboratories, said in the press release. “We have seen substantial progress in delivering treatment options for patients with advanced endometrial cancer with [pembrolizumab], 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.”


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. News release. Merck; March 21, 2022. Accessed March 22, 2022. https://bit.ly/3udt37j

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