Pembrolizumab/Chemo Gets FDA Priority Review in Endometrial Cancer

Female reproductive system diseases. Uterus cancer and endometrial malignant tumor as a uterine medical concept. 3D illustration: © Crystal Light - stock.adobe.com

• Pembrolizumab (Keytruda) plus chemotherapy was more effective than standard chemotherapy alone in treating primary advanced or recurrent endometrial cancer.
• The FDA has granted priority review to the supplemental biologics license application (sBLA) for pembrolizumab for the treatment of advanced endometrial cancer.
• If approved, pembrolizumab would be the first immunotherapy indicated for the frontline treatment of advanced endometrial cancer regardless of mismatch repair status.

The FDA has granted priority review to the sBLA of pembrolizumab and carboplatin/paclitaxel followed by pembrolizumab monotherapy for the treatment of patients with primary advanced or recurrent endometrial cancer.¹

The FDA has issued a Prescription Drug User Fee Act target action date of June 21, 2024.

“If approved, [pembrolizumab] would be the first immunotherapy indicated for the frontline treatment of advanced endometrial cancer regardless of mismatch repair status,” said Gursel Aktan, MD, PhD, vice president, global clinical development, Merck Research Laboratories, in a press release. “We are committed to working closely with the FDA to bring [pembrolizumab] to these patients who are in need of additional treatment options, and we thank our collaborators for their partnership on this study.”

The sBLA is supported by findings from the phase 3 NRG-GY018 study (NCT03914612) which were presented at the 2023 Society of Gynecologic Oncology meeting and published in the New England Journal of Medicine.² Compared with standard-of-care chemotherapy alone, pembrolizumab plus chemotherapy reduced the risk of disease progression or death by 46% (HR, 0.54; 95% CI, 0.41-0.71; P <.00001) among patients with mismatch repair (MMR) proficient (p) disease. In patients with MMR deficient (d) disease, the risk of disease progression or death was lowered by 70% (HR, 0.30; 95% CI, 0.19-0.48; P <.00001).

“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.¹ “The use of [pembrolizumab] in this setting has the potential to address a significant unmet need for these patients.”

About the NRG-GY018 Trial of Pembrolizumab and Chemotherapy in Endometrial Cancer

Findings from a 12-month analysis showed that the combination of pembrolizumab and chemotherapy delivered a progression-free survival (PFS) rate of 74% in the dMMR cohort (n = 225) vs 38% with placebo. In the pMMR cohort (n = 588), the median PFS was 13.1 months with pembrolizumab vs 8.7 months with placebo.²

“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, chief, division of Gynecologic Oncology, Washington University School of Medicine, told Targeted Oncology^TM.

Regarding safety, the safety profile of the combination was in line with previous reports. 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.

REFERENCES:

1. 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 February 20, 2024. http://tinyurl.com/yc2v3n3r

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