Pembrolizumab Prolongs PFS vs Chemotherapy in dMMR Endometrial Cancer

First-line pembrolizumab monotherapy prolonged progression-free survival (PFS) vs carboplatin plus paclitaxel in mismatch repair-deficient (dMMR) advanced or recurrent endometrial cancer, according to an interim analysis of the phase 3 KEYNOTE-C93/GOG-3064/ENGOT-en15 trial published online in the Lancet.

The investigators said a need exists for first-line chemotherapy-free options in this setting. The open-label, active-comparator controlled trial (NCT05173987) was conducted at 122 centers in 24 countries. PFS by blinded independent central review and overall survival (OS) were the primary end points.

A total of 299 adults with inoperable stage III or IV, persistent, advanced, or recurrent dMMR endometrial cancer were randomly assigned to intravenous pembrolizumab 400mg every 6 weeks for up to 18 cycles (n=149) or carboplatin plus paclitaxel every 3 weeks for 6 cycles (n=150). At the April 24, 2026, data cutoff, median PFS was 38.2 months with pembrolizumab vs 8.4 months with chemotherapy (hazard ratio, 0.57; 95% CI, 0.42-0.79).

Estimated PFS was 75% vs 76% at 6 months, 67% vs 40% at 12 months, and 53% vs 30% at 36 months. OS did not meet its prespecified significance criterion at the interim analysis; medians were not reached, and the confidence interval included no difference (hazard ratio, 0.77; 95% CI, 0.52-1.15).

Grade 3 or higher treatment-related adverse events occurred in 18% of the pembrolizumab group vs 51% of the chemotherapy group. Treatment-related adverse events led to discontinuation in 9% vs 15% and resulted in death in two participants receiving pembrolizumab (hepatic failure and bacterial meningitis) and one receiving chemotherapy (pulmonary embolism). Alopecia (2% vs 50%), anemia (5% vs 49%), and peripheral neuropathy (0% vs 26%) were more common with chemotherapy.

The investigators concluded that pembrolizumab produced a statistically significant and clinically meaningful PFS improvement with fewer treatment-related adverse events. They noted that the trial did not compare pembrolizumab monotherapy with the current standard of care of immunotherapy plus chemotherapy. The trial is ongoing.

Source: Slomovitz BM, Zhu J, Yin R, et al. First-line pembrolizumab versus carboplatin plus paclitaxel in participants with mismatch repair-deficient advanced or recurrent endometrial cancer (KEYNOTE-C93/GOG-3064/ENGOT-en15): interim analysis of a multicentre, open-label, randomised, active-comparator controlled, phase 3 trial. Lancet. Published online October 26, 2026. doi:10.1016/S0140-6736(26)02095-7