Trial results for pembrolizumab (Keytruda) in combination with chemotherapy for Stage III-IV or recurrent endometrial cancer were posted on ClinicalTrials.gov on 2025-03-18. The Phase 3 study (NCT03914612) indicated that in the pMMR cohort, the experimental arm achieved a median progression-free survival of 11.7 months compared to 8.7 months in the active comparator arm.
Background
The trial investigated the addition of the immunotherapy drug pembrolizumab to the usual chemotherapy treatment of paclitaxel and carboplatin for patients with Stage III-IV or recurrent endometrial cancer. The study included several types of endometrial cancer: Endometrial Clear Cell Adenocarcinoma, Endometrial Dedifferentiated Carcinoma, Endometrial Endometrioid Adenocarcinoma, Endometrial Mixed Cell Adenocarcinoma, and Endometrial Serous Adenocarcinoma.
Trial design
The study (NCT03914612) was a Phase 3 trial that enrolled 813 participants. It evaluated the combination of pembrolizumab, paclitaxel, and carboplatin against paclitaxel and carboplatin alone in patients with Stage III-IV or recurrent endometrial cancer. The conditions studied included Endometrial Clear Cell Adenocarcinoma, Endometrial Dedifferentiated Carcinoma, Endometrial Endometrioid Adenocarcinoma, Endometrial Mixed Cell Adenocarcinoma, and Endometrial Serous Adenocarcinoma. The trial compared an experimental arm receiving pembrolizumab, paclitaxel, and carboplatin with an active comparator arm receiving placebo, paclitaxel, and carboplatin.
Key results
The trial reported key measurements for progression-free survival (PFS), adverse events, and objective tumor response, stratified by dMMR and pMMR cohorts.
- Progression-free Survival (PFS):
- In the pMMR Cohort, the median PFS was 11.7 Months for the experimental arm (pembrolizumab, paclitaxel, carboplatin) compared to 8.7 Months for the active comparator arm (placebo, paclitaxel, carboplatin).
- In the dMMR Cohort, the median PFS was NA Months for the experimental arm (pembrolizumab, paclitaxel, carboplatin) compared to 7.6 Months for the active comparator arm (placebo, paclitaxel, carboplatin).
- Adverse Events With Grade 3 (or Higher):
- In the pMMR Cohort, 151 Participants in the experimental arm experienced Grade 3 or higher adverse events, compared to 124 Participants in the active comparator arm.
- In the dMMR Cohort, 68 Participants in the experimental arm experienced Grade 3 or higher adverse events, compared to 50 Participants in the active comparator arm.
- Objective Tumor Response:
- In the pMMR Cohort, 150 Participants in the experimental arm showed an objective tumor response, compared to 136 Participants in the active comparator arm.
- In the dMMR Cohort, 75 Participants in the experimental arm showed an objective tumor response, compared to 65 Participants in the active comparator arm.
What this means
The results suggest that adding pembrolizumab to chemotherapy may extend median progression-free survival in patients with pMMR Stage III-IV or recurrent endometrial cancer. While the median PFS for the dMMR cohort's experimental arm is not available, the pMMR data indicates a potential benefit. The observed increase in Grade 3 or higher adverse events in the experimental arms across both cohorts suggests a need for careful consideration of the risk-benefit profile when combining pembrolizumab with chemotherapy in this patient population. The higher number of objective tumor responses in the experimental arms also supports a potential clinical benefit.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT03914612, titled "Testing the Addition of the Immunotherapy Drug Pembrolizumab to the Usual Chemotherapy Treatment (Paclitaxel and Carboplatin) in Stage III-IV or Recurrent Endometrial Cancer," were posted on 2025-03-18 on clinicaltrials.gov.