Pembrolizumab Alone Exceeds Chemo in First-Line dMMR Endometrial Cancer

In an interview with Targeted Oncology, Brian M. Slomovitz, MD, of Mount Sinai Medical Center in Florida, discusses the results from the phase 3 KEYNOTE-C93/GOG-3064/ENGOT-en15 trial (NCT05173987) of pembrolizumab (Keytruda) for endometrial cancer, presented at the 2026 ESMO Congress.

In the trial, first-line pembrolizumab (Keytruda) monotherapy significantly improved progression-free survival (PFS) vs carboplatin plus paclitaxel in patients with mismatch repair–deficient (dMMR) advanced or recurrent endometrial carcinoma, with a median PFS by blinded independent central review of 38.2 months vs 8.4 months (HR, 0.57; 95% CI, 0.42-0.79; P = .0002).

Overall survival (OS) showed a favorable trend, with 36-month OS rates of 70.7% vs 62.0% (HR, 0.77; 95% CI, 0.52-1.15). Grade 3 or higher treatment-related adverse events occurred in 18.1% vs 50.7% of patients, and global health status/quality-of-life scores improved with pembrolizumab, with a between-group difference of 7.02 at week 12.

Slomovitz acknowledges that the chemotherapy-alone comparator was a limitation. The trial opened and closed before data supporting first-line chemoimmunotherapy emerged. Which patients should receive pembrolizumab alone rather than chemoimmunotherapy remains unclear. Slomovitz explains that the benefit curves cross at about 6 months and then separate durably in favor of pembrolizumab. This suggests that some patients benefit from chemotherapy early on, whereas many do not need it. He says that subsequent trials could be needed to better identify the subset of patients who do require chemotherapy.

Crossover likely affected the OS results. In the chemotherapy arm, 85.2% of patients with progression received pembrolizumab through crossover or another PD-1/PD-L1 inhibitor off study. According to Slomovitz, sensitivity analyses suggested that this crossover diluted the OS HR, making this essentially a study of pembrolizumab in the first vs second line of therapy, explaining the weaker OS findings.

REFERENCES

Slomovitz BM, Backes F, Mackowiak-Matejczyk B, et al. KEYNOTE-C93/GOG-3064/ENGOT-en15: Phase 3, randomized, open-label study of first-line (1L) pembrolizumab (pembro) vs carboplatin (C) + paclitaxel (P) in mismatch repair-deficient (dMMR) advanced or recurrent endometrial carcinoma (a/rEC). Presented at: 2026 ESMO Congress; October 23-27, 2026; Madrid, Spain. Abstract LBA12.