Pembrolizumab Plus Chemotherapy Under Review for Primary Advanced or Recurrent Endometrial Cancer

The Food and Drug Administration (FDA) has accepted for Priority Review the supplemental Biologics License Application (sBLA) for pembrolizumab, in combination with standard of care chemotherapy, followed by pembrolizumab as a single agent for the treatment of patients with primary advanced or recurrent endometrial carcinoma. 

Pembrolizumab, an anti-programmed death receptor-1 therapy, is marketed under the brand name Keytruda and is currently approved for 2 endometrial carcinoma indications:

• In combination with lenvatinib, for the treatment of patients with advanced endometrial carcinoma that is mismatch repair proficient (pMMR) as determined by an FDA-approved test, or not microsatellite instability-high (MSI-H), who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation; and
• As a single agent, for the treatment of patients with advanced endometrial carcinoma that is MSI-H or mismatch repair deficient (dMMR), as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.

The sBLA is supported by data from the phase 3 NRG-GY018 trial (ClinicalTrials.gov Identifier: NCT03914612), which compared the efficacy and safety of pembrolizumab plus chemotherapy (carboplatin and paclitaxel) to chemotherapy alone for the first-line treatment of patients with stage III-IV or recurrent endometrial carcinoma whose cancer was either pMMR or dMMR. The primary endpoint was progression free survival (PFS). 

In the pMMR cohort (n=591), treatment with pembrolizumab plus chemotherapy reduced the risk of disease progression or death by 46% vs chemotherapy alone (hazard ratio [HR], 0.54 [95% CI, 0.41-0.71]; P <.00001), after a median follow-up of 7.9 months; median PFS was 13.1 months vs 8.7 months, respectively.

In the dMMR cohort (n=225), treatment with pembrolizumab plus chemotherapy reduced the risk of disease progression or death by 70% vs chemotherapy alone (HR, 0.30 [95% CI, 0.19-0.48]; P <.00001), after a median follow-up of 12 months; median PFS was not reached in the pembrolizumab arm vs 7.6 months in the chemotherapy arm.

The safety profile of pembrolizumab was consistent with that seen in previous trials and no new safety signals were identified.

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

A Prescription Drug User Act target date of June 21, 2024 has been assigned to the application.

This article originally appeared on MPR