FDA Approves Pembrolizumab Plus Chemo for Endometrial Cancer

• Pembrolizumab (Keytruda) plus chemotherapy is now an approved combination for primary advanced or recurrent endometrial carcinoma, regardless of mismatch repair (MMR) status.
• The approval marks the first immunotherapy cleared for use in the frontline treatment of this disease state regardless of MMR status.
• Pembrolizumab plus chemotherapy improved survival vs chemotherapy alone, according to findings from the phase 3 NRG-GY018/KEYNOTE-868 study (NCT03914612).

The FDA has approved the combination of pembrolizumab and standard-of-care chemotherapy followed by single-agent pembrolizumab for the treatment of patients with primary advanced or recurrent endometrial cancer.¹

This approval makes pembrolizumab the first immunotherapy indicated for the frontline treatment of advanced endometrial cancer, regardless of MMR status.

The approval is supported by data from the phase 3 NRG-GY018/KEYNOTE-868 study. Results presented at the 2023 Society of Gynecologic Oncology Annual Meeting and published in The New England Journal of Medicine showed that the Kaplan-Meier estimates of progression-free survival (PFS) in the MMR-deficient (dMMR) was 74% in the pembrolizumab plus chemotherapy arm vs 38% in the placebo plus chemotherapy arm (HR, 0.30; 95% CI, 0.19-0.48; P <.001), demonstrating a 70% difference in relative risk.² In the MMR-proficient (pMMR) cohort, the median PFS was 13.1 months with pembrolizumab vs 8.7 months with placebo (HR, 0.54; 95% CI, 0.51-0.71; P <.001).

“The main findings were an improvement in the progression-free and overall survival for the addition of pembrolizumab to standard chemotherapy with acceptable toxicity,” said Matthew Powell, MD, Ira C. and Judith Gall Distinguished Professor of Obstetrics and Gynecology at Washington University School of Medicine in St. Louis, told Targeted Oncology^TM.

The safety profile was consistent with the known profiles of pembrolizumab and chemotherapy. Patients treated with pembrolizumab experienced more grade 3 or greater adverse effects in both the dMMR (63.3% vs 55.1%) and pMMR (47.2% vs 45.3%) cohorts.

“Endometrial cancer is the most common type of gynecological cancer, and frontline treatment options are limited for patients with advanced stage or recurrent disease,” said Ramez Eskander, MD, principal investigator and gynecologic oncologist, University of California San Diego, Moores Cancer Center, in a press release.³ “The use of [pembrolizumab] in this setting has the potential to address a significant unmet need for these patients.”

The application of this combination was granted priority review in February 2024.³

REFERENCES:

1. FDA approves pembrolizumab with chemotherapy for primary advanced or recurrent endometrial carcinoma. News release. US FDA. June 17, 2024. Accessed June 17, 2024. https://tinyurl.com/47p6cwy2

2. Eskander RN, Sill MW, Beffa L, et al. Pembrolizumab plus chemotherapy in advanced endometrial cancer. N Engl J Med. 2023;388(23):2159-2170. doi:10.1056/NEJMoa2302312

3. FDA grants priority review to Merck’s application for Keytruda (pembrolizumab) plus chemotherapy as treatment for primary advanced or recurrent endometrial carcinoma. News release. Merck. February 20, 2024. Accessed April 23, 2024. http://tinyurl.com/yc2v3n3r