In the KEYNOTE-B21 study, adjuvant pembrolizumab (Keytruda; Merck) in combination with chemotherapy, with or without radiotherapy, did not meet its primary end points of disease-free survival (DFS) for patients with newly diagnosed high-risk endometrial cancer after surgery with curative intent, according to a news release. The study’s co-primary endpoint of overall survival (OS) was not formally tested due to DFS not being reached.1
“While these results were not what we had hoped, we are focused on continuing to build on the established role of [pembrolizumab] in advanced endometrial carcinoma through our approved indications, while rapidly progressing clinical research evaluating [pembrolizumab]-based combinations and other investigational candidates, including antibody-drug conjugates, in endometrial and other types of gynecologic malignancies,” Gursel Aktan, MD, PhD, vice president of global clinical development at Merck Research Laboratories, said in the press release. “We would like to thank all the patients, the investigators, and our study collaborators for their participation in this trial.”1
According to the American Cancer Society, the estimates for endometrial cancer in the United States for 2024 are about 67,880 newly diagnosed cases and 13,250 deaths from the cancer.2
The safety profile of pembrolizumab was consistent with those previously reported and no new safety singles were identified. An evaluation of the study data is ongoing and the company will share the results, according to the news release.1
Key Takeaways
- The pembrolizumab combination did not improve disease-free survival (DFS), the primary endpoint of the study.
- Overall survival (OS) was not formally analyzed due to the DFS results.
- Pembrolizumab is already approved for advanced endometrial cancer that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), in combination with lenvatinib. It is also approved as a single agent for MSI-H/dMMR advanced endometrial cancer that has progressed after other treatments.
In 2021, the FDA approved pembrolizumab 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) as the first indication for the drug in the endometrial space. The approval was based on the results from the KEYNOTE-775 trial, which confirmed the clinical benefit of an accelerated approval including 827 individuals who were previously treated with at least 1 period platinum-based chemotherapy regimen. In the trial, median progression free survival (PFS) with pembrolizumab was 6.6 months compared to the investigator’s choice regimen of 3.8 months. The OS was 17.4 months compared to 12 months, with an overall response rate (ORR) of 30% and 15%, respectively.3
In 2022, the FDA also approved pembrolizumab as a single agent for patients who had MSI-H or dMMR advanced endometrial carcinoma and experienced disease progression after prior systemic therapy in any setting, but were not candidates for surgery or radiation. This approval was based on results from cohorts D and K of the KEYNOTE-158 trial (NCT02628067), which had a median of 16 months of follow up. The investigators found an ORR of 46% with a complete response rate of 12% and partial response of 33%. Duration of response lasted 12 months or longer for 68% of patients, with 44% having a response for 24 months or longer. Median PFS was 13.1 months and OS was not reached at the time of approval.4
References
Merck Provides Update on Phase 3 KEYNOTE-B21 Trial Evaluating Keytruda (pembrolizumab) Plus Chemotherapy, With or Without Radiotherapy, for Patients With Newly Diagnosed, High-Risk Endometrial Cancer After Surgery With Curative Intent. News release. Merck. May 9, 2024. Accessed May 10, 2024. https://www.merck.com/news/merck-provides-update-on-phase-3-keynote-b21-trial-evaluating-keytruda-pembrolizumab-plus-chemotherapy-with-or-without-radiotherapy-for-patients-with-newly-diagnosed-high-risk-endometrial-c/
American Cancer Society. Key Statistics for Endometrial Cancer. Updated January 17, 2024. Accessed May 10, 2024. https://www.cancer.org/cancer/types/endometrial-cancer/about/key-statistics.html
Hippensteele A. FDA Approves Pembrolizumab, Lenvatinib Combination Therapy for Advanced Endometrial Carcinoma. Pharmacy Times. July 2022, 2021. Accessed May 10, 2024. https://www.pharmacytimes.com/view/fda-approves-pembrolizumab-lenvatinib-combination-therapy-for-advanced-endometrial-carcinoma
Pharmacy Times. FDA Approves Pembrolizumab for MSI‑H/dMMR Advanced Endometrial Carcinoma. March 22, 2022. Accessed May 10, 2024. https://www.pharmacytimes.com/view/fda-approves-pembrolizumab-for-msi-h-dmmr-advanced-endometrial-carcinoma
