FDA Grants Priority Review to Pembrolizumab/Chemo in Endometrial Cancer


Data from the phase 3 NRG-GY018 trial support the supplemental biologics license application for pembrolizumab plus chemotherapy as a treatment for those with primary advanced or recurrent endometrial cancer.

FDA Grants Priority Review to Pembrolizumab/Chemo in Endometrial Cancer | Image Credit: © freshidea - stock.adobe.com.

“The use of [pembrolizumab] in this setting has the potential to address a significant unmet need for these patients," according to Ramez Eskander, MD.

The FDA has granted priority review to a supplemental biologics application (sBLA) for pembrolizumab (Keytruda) plus standard chemotherapy followed by pembrolizumab as a treatment for patients with primary advanced or recurrent endometrial cancer, according to a press release from Merck.1

The regulatory agency has set a Prescription Drug User Fee Act date of June 21, 2024, for its decision on approving the pembrolizumab-based combination in this indication.

Supporting data for the sBLA came from the phase 3 NRG-GY018 trial (NCT03914612). Investigators presented results from the trial at the 2023 Annual Global Meeting of the International Gynecologic Cancer Society (IGCS) and published their findings in The New England Journal of Medicine.

Among patients with mismatch repair–deficient (dMMR) disease, the risk of disease progression or death was reduced by 70% in the pembrolizumab arm vs the placebo arm (HR, 0.30; 95% CI, 0.19-0.48; P <.001).2 At 12 months, the estimated progression-free survival (PFS) rates were 74% with pembrolizumab vs 38% with placebo.

With a median follow-up of 7.9 months among patients with mismatch repair–proficient (pMMR) disease, the median PFS was 13.1 months in patients who received pembrolizumab compared with 8.7 months in those who received placebo (HR, 0.54; 95% CI, 0.41-0.71; P <.001). Subgroup analyses appeared to highlight a PFS benefit with pembrolizumab plus chemotherapy across the dMMR and pMMR cohorts, although investigators noted some subgroups were small and that findings were heterogenous with respect to geographic location.

Any-grade adverse effects (AEs) in the dMMR cohort affected 98.2% of patients in the pembrolizumab arm and 99.1% of those in the placebo arm. The rates of any-grade toxicities in each respective arm were 93.5% vs 93.4% in the pMMR cohort. The safety profile of pembrolizumab and combination chemotherapy in the NRG-GY018 trial was comparable with prior reports of each individual agent.

“Endometrial cancer is the most common type of gynecological cancer, and frontline treatment options are limited for patients with advanced stage or recurrent disease,” lead investigator Ramez Eskander, MD, gynecologic oncologist at the University of California San Diego Moores Cancer Center, said in the press release.1 “The use of [pembrolizumab] in this setting has the potential to address a significant unmet need for these patients.”

In the double-blind phase 3 trial, 816 patients with advanced or recurrent (stage III or IVA) endometrial cancer were randomly assigned to receive pembrolizumab at 200 mg intravenously or placebo plus chemotherapy followed by maintenance with pembrolizumab at 400 mg or placebo. Chemotherapy consisted of paclitaxel plus carboplatin.

The trial’s primary end point was investigator-assessed PFS based on RECIST criteria. Secondary end points included OS, safety, and health-related quality of life.

Patients 18 years and older with confirmed advanced, metastatic, or recurrent endometrial cancer of any histology apart from carcinosarcoma were able to enroll on the trial. Other eligibility criteria included having measurable stage III or IVA disease based on RECIST guidelines or stage IVB or recurrent endometrial cancer with or without measurable disease.

“If approved, [pembrolizumab] would be the first immunotherapy indicated for the frontline treatment of advanced endometrial cancer regardless of mismatch repair status,” Gursel Aktan, PhD, vice president of Global Clinical Development at Merck Research Laboratories, said in the press release.1 “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.”


  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/5hc2vunb
  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
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