FDA Approves Pembrolizumab Plus Chemo for Advanced or Recurrent Endometrial Cancer

The FDA has approved pembrolizumab (Keytruda) in combination with carboplatin and paclitaxel, followed by single-agent pembrolizumab, for the treatment of adult patients with primary advanced or recurrent endometrial carcinoma.

The approval was based on findings from the KEYNOTE-868/NRG-GY018 trial (NCT03914612), according to the notice from the FDA. In this multicenter, randomized, double-blind, placebo-controlled trial, researchers enrolled 810 patients with advanced or recurrent endometrial carcinoma. Patients were grouped by mismatch repair (MMR) status: 588 patients were in the mismatch repair proficient (pMMR) cohort and 222 patients were in the mismatch repair deficient (dMMR) cohort.

Patients in the trial were randomized 1:1 to receive one of the following treatments:

• 200 mg of pembrolizumab every 3 weeks, 175 mg/m² of paclitaxel, and carboplatin AUC 5 mg/mL/min for 6 cycles, followed by 400 mg of pembrolizumab every 6 weeks for up to 14 cycles.
• placebo every 3 weeks, 175 mg/m² of paclitaxel and carboplatin AUC 5 mg/mL/min for 6 cycles, followed by placebo every 6 weeks for up to 14 cycles.

Of note, randomization was stratified by ECOG performance status (0 or 1 vs 2), MMR status, and prior adjuvant chemotherapy.

The major efficacy outcome measure for this trial was progression-free survival (PFS) per RECIST 1.1 criteria.

For patients in the dMMR cohort, the median PFS was not reached (NR; 95% CI, 30.7-NR) in those assigned pembrolizumab plus chemotherapy, compared with 6.5 months (95% CI, 6.4-8.7) in those assigned placebo plus chemotherapy (HR = 0.30; 95% CI, 0.19-0.48; P < .0001). In the pMMR cohort, median PFS was 11.1 months (95% CI, 8.7-13.5) vs 8.5 months (95% CI, 7.2-8.8), respectively (HR = 0.60; 95% CI, 0.46-0.78; P < .0001).

Patients assigned pembrolizumab plus chemotherapy experienced similar adverse reactions to those previously reported, with the exception of a higher incidence of rash, according to the notice.

The recommended dose for pembrolizumab is 200 mg every 3 weeks or 400 mg every 6 weeks until unacceptable toxicity, disease progression, or up to 24 months.

Reference

FDA approves pembrolizumab with chemotherapy for primary advanced or recurrent endometrial carcinoma. News release. FDA. June 17, 2024. Accessed June 17, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-chemotherapy-primary-advanced-or-recurrent-endometrial-carcinoma