FDA approves pembrolizumab with chemotherapy for primary advanced or recurrent endometrial carcinoma

Regulatory approval: On June 17, 2024, the FDA approved pembrolizumab plus carboplatin/paclitaxel, followed by single-agent pembrolizumab, for adult patients with primary advanced or recurrent endometrial carcinoma. Approval was supported by KEYNOTE-868/NRG-GY018, which showed improved investigator-assessed PFS versus placebo plus chemotherapy in both dMMR (HR 0.30) and pMMR (HR 0.60) cohorts. Rash occurred more often with pembrolizumab plus chemotherapy.

FDA approval (June 17, 2024)

The US Food and Drug Administration (FDA) approved pembrolizumab (Keytruda; Merck) in combination with carboplatin and paclitaxel, followed by single-agent pembrolizumab, for adult patients with primary advanced or recurrent endometrial carcinoma.

Supporting evidence: KEYNOTE-868/NRG-GY018 (NCT03914612)

This multicenter, randomized, double-blind, placebo-controlled trial enrolled 810 patients with advanced or recurrent endometrial carcinoma, with separate cohorts by mismatch repair (MMR) status: dMMR (n=222) and pMMR (n=588). Patients were randomized 1:1 to:

  • Pembrolizumab 200 mg q3w + paclitaxel 175 mg/m² + carboplatin AUC 5 for 6 cycles, then pembrolizumab 400 mg q6w up to 14 cycles, or
  • Placebo on the same schedule with chemotherapy. Stratification factors included MMR status, ECOG PS (0–1 vs 2), and prior adjuvant chemotherapy.

Primary efficacy outcome: investigator-assessed PFS per RECIST 1.1.

  • dMMR cohort: median PFS NR (95% CI 30.7–NR) vs 6.5 months (95% CI 6.4–8.7); HR 0.30 (95% CI 0.19–0.48); p<0.0001.
  • pMMR cohort: median PFS 11.1 months (95% CI 8.7–13.5) vs 8.5 months (95% CI 7.2–8.8); HR 0.60 (95% CI 0.46–0.78); p<0.0001.

Safety and dosing

Adverse reactions were generally consistent with known profiles for pembrolizumab and chemotherapy, with a higher incidence of rash reported. Recommended pembrolizumab dosing is 200 mg q3w or 400 mg q6w until progression, unacceptable toxicity, or up to 24 months.

Regulatory context

The review was conducted under Project Orbis with collaboration from other agencies; reviews at partner agencies were ongoing at the time of the FDA announcement.

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