The Food and Drug Administration (FDA) has approved Keytruda® (pembrolizumab) as a single agent 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. The VENTANA MMR RxDx Panel was also approved as a companion diagnostic device to select patients with dMMR in solid tumors that are eligible for treatment with pembrolizumab.
The approval was based on data from the open-label, multicohort phase 2 KEYNOTE-158 trial (ClinicalTrials.gov Identifier: NCT02628067), which evaluated pembrolizumab in patients with multiple types of advanced solid tumors. Cohorts D and K included 90 patients with MSI-H or dMMR endometrial carcinoma.
Patients received pembrolizumab 200mg intravenously every 3 weeks until unacceptable toxicity or documented disease progression. The major efficacy outcome measures were objective response rate (ORR) and duration of response (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.
Based on a median follow-up time of 16 months (range 0.5 to 62.1 months), results showed an ORR of 46% (95% CI, 35-56) among the 90 patients, with 12% achieving complete response and 33% achieving partial response. The median DoR was not reached (95% CI, 2.9-55.7+ months), with 68% of patients having a response duration of at least 12 months and 44% having a response duration of at least 24 months.
When used as a single agent, the most common adverse reactions reported with pembrolizumab include fatigue, musculoskeletal pain, rash, diarrhea, pyrexia, cough, decreased appetite, pruritus, dyspnea, constipation, pain, abdominal pain, nausea, and hypothyroidism.
Keytruda, a programmed death receptor-1 blocking antibody, is also indicated in combination with lenvatinib, for the treatment of patients with advanced endometrial carcinoma that is not MSI-H or dMMR, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
- 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 & Co., Inc. March 21, 2022. https://www.merck.com/news/fda-approves-mercks-keytruda-pembrolizumab-for-patients-with-msi%E2%80%91h-dmmr-advanced-endometrial-carcinoma-who-have-disease-progression-following-prior-systemic-therapy-in-any-se/
- FDA approves pembrolizumab for advanced endometrial carcinoma. News release. March 21, 2022. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-advanced-endometrial-carcinoma
- Keytruda. Package insert. Merck & Co., Inc.; 2022. Accessed March 22, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/125514s110lbl.pdf