FDA Approves Merck’s Keytruda in Combination with Carboplatin and Paclitaxel to Treat Advanced or Recurrent Endometrial Carcinoma

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The FDA has approved Merck’s Keytruda (pembrolizumab) in combination with carboplatin and paclitaxel, followed by an additional dose of Keytruda, for the treatment of patients with primary advanced or recurrent endometrial carcinoma. According to the company, the approval was based on promising results from the Phase III NRG-GY018/KEYNOTE-868 clinical trial, which found that the combination of Keytruda with carboplatin and paclitaxel followed by solo Keytruda significantly reducedthe risk of disease progression or death in patients whose cancer was mismatch repair proficient (pMMR) or mismatch repair deficient (dMMR) compared to placebo with chemotherapy alone.¹

“This is the first Phase III trial to statistically evaluate an anti-PD-1 immunotherapy plus chemotherapy combination in patients with pMMR and dMMR tumors as two independent cohorts,” said Ramez N. Eskander, MD, principal investigator, associate professor in the department of obstetrics, gynecology, and reproductive services, University of California San Diego School of Medicine, gynecologic oncologist, Moores Cancer Center at University of California San Diego Health, in a press release. “The addition of pembrolizumab to chemotherapy represents a new frontline therapeutic option for patients with primary advanced or recurrent endometrial carcinoma, demonstrating a statistically significant and clinically meaningful progression-free survival benefit compared to chemotherapy alone, regardless of mismatch repair status.”

NRG-GY018/KEYNOTE-868 is a multicenter, randomized, double-blind, placebo-controlled trial (NCT03914612) that evaluated Keytruda in combination with carboplatin and paclitaxel in comparison to placebo plus carboplatin and paclitaxel. Investigators enrolled 810 patients with advanced or recurrent endometrial carcinoma, who were divided into two cohorts based on MMR status. A total of 222 patients were enrolled in the dMMR cohort and 588 patients were enrolled in the pMMR cohort. Patients were randomly assigned to receive either 200 mg of Keytruda every three weeks plus 175 mg of paclitaxel and 5 mg of carboplatin for six cycles, with an addition of 400 mg of Keytruda every six weeks for up to 14 cycles, or placebo plus paclitaxel and carboplatin every three weeks for six cycles, followed by six weeks of placebo for 14 cycles.

The results demonstrated that Keytruda plus carboplatin and paclitaxel followed by Keytruda reduced the risk of disease progression or death by 40% in pMMR patients. Additionally, the combination was found to reduce the risk of disease progression or death by 70% in dMMR patients. The typical median duration of exposure to Keytruda was 5.6 months.

Adverse events (AEs) resulted in discontinuation for 14% of the study’s participants. Further, significant AEs were reported in 35% of participants treated with the Keytruda combination and 19% in those treated with the placebo. Fatal AEs occurred in 1.6% of patients administered Keytruda, which included cardiac arrest and complications associated with COVID-19. The most common AEs included fatigue, diarrhea, rash, and nausea, with diarrhea being the most common at 28%.¹

“Endometrial cancer is now the most common gynecologic cancer in the U.S., and deaths from the disease are projected to surpass deaths from ovarian cancer in 2024, underscoring the need for treatment advances for more patients,” said Gursel Aktan, MD, PhD, VP, global clinical development, Merck Research Laboratories, in the press release. “This approval represents the first and only anti-PD-1-based option for adult patients with primary advanced or recurrent endometrial carcinoma regardless of mismatch repair status, building on the established role of Keytruda in certain types of advanced endometrial carcinoma as monotherapy and in combination with Lenvima.”

Reference

1. FDA Approves Merck’s KEYTRUDA® (pembrolizumab) Plus Carboplatin and Paclitaxel as Treatment for Adult Patients With Primary Advanced or Recurrent Endometrial Carcinoma. Merck. June 17, 2024. Accessed June 18, 2024. https://www.merck.com/news/fda-approves-mercks-keytruda-pembrolizumab-plus-carboplatin-and-paclitaxel-as-treatment-for-adult-patients-with-primary-advanced-or-recurrent-endometrial-carcinoma/