Real-world outcomes of first-line pembrolizumab monotherapy among dMMR/MSI-H advanced or recurrent endometrial cancer patients in the United States

Objective: Describe real-world outcomes among patients with dMMR/MSI-H advanced or recurrent endometrial cancer (EC) treated with first-line (1 L) pembrolizumab monotherapy or carboplatin–paclitaxel. Methods: This retrospective cohort study used the Flatiron Health Research Database (January 1, 2013–June 30, 2025). Adult patients with dMMR/MSI-H advanced or recurrent EC who initiated pembrolizumab monotherapy or carboplatin–paclitaxel as 1 L therapy on or after May 1, 2017, were included. Real-world time on treatment (rwTOT) and time to next treatment or death (rwTTNT) were estimated using Kaplan–Meier methods overall and by prior neoadjuvant/adjuvant platinum therapy. Results: Of the 228 patients included, 80 received pembrolizumab and 148 carboplatin–paclitaxel. Median age ranged from 65 to 70 years; most patients had endometrioid histology (86.3%) and recurrent disease (78.8%). Among patients with prior neoadjuvant/adjuvant platinum therapy n = 41, 75.6% (n = 31) received pembrolizumab and (n = 10) 24.4% received carboplatin–paclitaxel. Median rwTOT (months) was 9.1 (95% CI: 5.1–14.5) for pembrolizumab and 3.5 (95% CI: 3.4–3.5) for carboplatin–paclitaxel. Median rwTTNT was 16.6 (95% CI: 9.4–32.3) for pembrolizumab and 5.8 (95% CI: 5.4–6.2) for carboplatin–paclitaxel. Among patients with prior platinum therapy, rwTOT and rwTTNT were 12.2 (95% CI: 4.9–23.5) and 23.1 (95% CI: 7.2–NE) for pembrolizumab, and 3.1 (95% CI: 0.0–3.7) and 5.4 (95% CI: 1.9–15.2) for carboplatin–paclitaxel. Conclusions: These real-world findings suggest pembrolizumab may be an effective chemotherapy-free option for patients with dMMR/MSI-H advanced or recurrent EC. Confirmatory evidence from the ongoing KEYNOTE-C93 trial (NCT05173987) will help inform its efficacy in this setting.