FDA Approves Pembrolizumab for Select Patients With MSI-H/dMMR Advanced Endometrial Carcinoma

Pembrolizumab (Keytruda) has been granted approval by the FDA for the treatment of patients with advanced endometrial carcinoma that is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.¹ 

The approval is based on new data from cohorts D and K of the KEYNOTE-158 trial (NCT02628067) which revealed the objective response rate (ORR) to be 46% (95% CI, 35-56) for patients who received pembrolizumab.

“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,” said David O’Malley, MD, Division of Gynecologic Oncology, The Ohio State University Wexner Medical Center and The James Comprehensive Cancer Center, 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.”

The multicenter, non-randomized, open-label, multi-cohort trial, KEYNOTE-158, enrolled 90 patients with unresectable or metastatic MSI-H or dMMR endometrial carcinoma into cohorts D or K and received at least one dose of pembrolizumab.²

For eligibility in enrollment, patients must have failed at least 1 line of standard of care systemic therapy with the exception of colorectal carcinoma (CRC) participants who must have failed at least 2 lines of standard of care systemic therapy, as per CRC specific eligibility criteria. Participants must not have melanoma or non-small cell lung cancer.

Other requirements included progression of tumor or intolerance to therapies known to provide clinical benefit, radiologically-measurable disease, an ECOG performance status of 0 or 1, adequate organ function, and tumor tissue supplied for study analyses.

The primary end point of the trial was objective response rate, and secondary end points consisted of duration of response (DOR), progression-free survival, and overall survival.

Patients were given pembrolizumab at 200 mg intravenously every 3 weeks until unacceptable toxicity or until disease progression was documented. Patients could be treated with pembrolizumab for up to 24 months if they did not have disease progression. Additionally, tumor status was assessed every 9 weeks for the first 12 months, and every 12 weeks after.

Of the 90 patients with MSI-H or dMMR endometrial carcinoma enrolled in the study who were treated with pembrolizumab, the median duration of exposure to pembrolizumab was 8.3 months (range, 1 day to 26.9 months).

The ORR of 46% for patients who received pembrolizumab includes a complete response rate of 12% and a partial response rate of 33% at a median follow-up time of 16.0 months (range, 0.5 to 62.1 months). Of the responding patients (n = 41), 68% had responses lasting 12 months or longer, and 44% had responses lasting 24 months or longer. Median DOR was not reached (range, 2.9 to 55.7+ months).

In regard to safety, adverse reactions occurring in patients with endometrial carcinoma were similar to those occurring in 2,799 patients with melanoma or non-small cell lung cancer treated with pembrolizumab as a single agent. The most common adverse events (≥20%) included fatigue, musculoskeletal pain, rash, diarrhea, pyrexia, cough, decreased appetite, pruritus, dyspnea, constipation, pain, abdominal pain, nausea, and hypothyroidism.

REFERENCES:

1. 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 21, 2022.

2. Study of Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3475-158/KEYNOTE-158). Clinicaltrials.gov. Accessed March 21, 2022. https://clinicaltrials.gov/ct2/show/NCT02628067