Pembrolizumab/Chemo Misses on Disease-Free Survival in Endometrial Cancer

Pembrolizumab (Keytruda) plus adjuvant chemotherapy with or without radiotherapy did not improve disease-free survival (DFS) in patients with newly diagnosed, high-risk endometrial cancer, missing the primary end point of the phase 3 KEYNOTE-B21 study (NCT04634877).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,” said Gursel Aktan, MD, PhD, vice president, global clinical development, Merck Research Laboratories, in a press release.

A prespecified interim analysis for KEYNOTE-B21 was planned. Here, it was observed that the data for pembrolizumab plus chemotherapy with or without radiotherapy did not meet the statistical criteria for DFS compared with placebo plus chemotherapy with or without radiotherapy. The dual primary end point of overall survival (OS) was not analyzed as DFS was not reached.

The safety profile of pembrolizumab was consistent with previous reports, and no new safety signals were identified.

Pembrolizumab is currently FDA-approved in 2 endometrial cancer indications: in combination with lenvatinib (Lenvima) in mismatch repair-proficient (pMMR) or not microsatellite instability-high (MSI-H) advanced endometrial cancer that has progressed following prior therapy or as a single agent in MSI-H or MMR deficient endometrial cancer that has progressed following prior therapy and is not suitable for surgery or radiation.

In February 2023, Merck announced findings from the KEYNOTE-868/NRG-GY018 study (NCT03914612) that pembrolizumab plus carboplatin and paclitaxel improved progression-free survival in patients with stage III to IV or recurrent endometrial cancer, regardless of MMR status.² Additionally, data presented at the 2024 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer in March showed that this combination improved OS in the intent-to-treat population.³

The FDA granted priority review for the supplemental biologic license supported by KEYNOTE-868, and the Prescription Drug User Fee Act target action date of June 21, 2024.¹

REFERENCES:

1. 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 9, 2024. https://tinyurl.com/3adss9uw

2. Merck’s KEYTRUDA® (pembrolizumab) plus chemotherapy met primary endpoint of progression-free survival (PFS) as first-line therapy for advanced or recurrent endometrial carcinoma. News release. Merck. February 3, 2023. Accessed May 9, 2024. https://bit.ly/3l9DkAw

3. Eskander RN, Sill M, Miller A, et al. Overall survival, progression-free survival by PD-L1 status, and blinded independent central review results with pembrolizumab plus carboplatin/paclitaxel (CP) versus placebo plus CP in patients with endometrial cancer: results from the NRG GY018 trial. Presented at: Society of Gynecologic Oncology 2024 Annual Meeting for Women’s Cancer; March 15-18, 2024; San Diego, CA.