Pembrolizumab Phase 3 for pMMR Endometrial Cancer: 11.7 Months Median PFS

A PHASE3 trial investigating Pembrolizumab (Keytruda) in combination with chemotherapy for stage III-IV or recurrent endometrial cancer completed primary data collection on 2022-12-16. The study reported a median progression-free survival of 11.7 Months in the pMMR cohort when Pembrolizumab was added to standard chemotherapy, compared to 8.7 Months with chemotherapy alone.

Background

Pembrolizumab is an immunotherapy drug that may help the body's immune system target cancer cells. This PHASE3 trial evaluated its addition to the standard chemotherapy regimen of paclitaxel and carboplatin for patients with stage III-IV or recurrent endometrial cancer.

Trial design

The PHASE3 trial, NCT03914612, enrolled 813 participants with stage III-IV or recurrent endometrial cancer, including those with Endometrial Clear Cell Adenocarcinoma, Endometrial Dedifferentiated Carcinoma, Endometrial Endometrioid Adenocarcinoma, Endometrial Mixed Cell Adenocarcinoma, and Endometrial Serous Adenocarcinoma. Patients were stratified into dMMR (deficient mismatch repair) and pMMR (proficient mismatch repair) cohorts. The study compared the addition of pembrolizumab to the usual chemotherapy treatment of paclitaxel and carboplatin against chemotherapy alone (placebo, paclitaxel, carboplatin).

Key results

In the pMMR (proficient mismatch repair) cohort, the median Progression-free Survival (PFS) was 11.7 Months for patients receiving pembrolizumab plus chemotherapy, compared to 8.7 Months for those receiving chemotherapy alone.

For the dMMR (deficient mismatch repair) cohort, the median PFS was 7.6 Months in the active comparator arm (placebo, paclitaxel, carboplatin); the median PFS for the experimental arm was reported as NA Months.

Regarding safety, Adverse Events With Grade 3 (or Higher) occurred in 68 Participants in the dMMR experimental arm versus 50 Participants in the dMMR comparator arm. In the pMMR cohort, 151 Participants in the experimental arm experienced grade 3 or higher adverse events, compared to 124 Participants in the comparator arm.

Objective tumor response was observed in 75 Participants in the dMMR experimental arm versus 65 Participants in the dMMR comparator arm. In the pMMR cohort, 150 Participants in the experimental arm showed objective tumor response, compared to 136 Participants in the comparator arm.

What this means

The primary completion of this PHASE3 trial suggests that adding pembrolizumab to standard chemotherapy may improve progression-free survival for patients with pMMR stage III-IV or recurrent endometrial cancer, with a median PFS of 11.7 Months compared to 8.7 Months with chemotherapy alone. While the experimental arm showed a numerical increase in Grade 3 or higher adverse events and objective tumor responses in both cohorts, the inability to report a median PFS for the dMMR experimental arm prevents a direct comparison in that subgroup from this data.

Source

These trial completion details and preliminary outcome measurements were posted on ClinicalTrials.gov on 2022-12-16. The full study record for NCT03914612 is available on clinicaltrials.gov.