Pembrolizumab in Patients With Microsatellite Instability-High Advanced Endometrial Cancer: Results From the KEYNOTE-158 Study

Abstract

Purpose: Pembrolizumab demonstrated durable antitumor activity in patients with previously treated, advanced microsatellite instability-high or mismatch repair-deficient (MSI-H/dMMR) tumors, including endometrial cancer, in the nonrandomized, open-label, multicohort, phase II KEYNOTE-158 study (NCT02628067). We report efficacy and safety outcomes for patients with MSI-H/dMMR endometrial cancer enrolled in KEYNOTE-158.

Methods: Eligible patients from cohorts D (endometrial cancer, regardless of MSI-H/dMMR status) and K (any MSI-H/dMMR solid tumor, except colorectal) with previously treated, advanced MSI-H/dMMR endometrial cancer received pembrolizumab 200 mg once every 3 weeks for 35 cycles. The primary end point was objective response rate per RECIST version 1.1 by independent central radiologic review. Secondary end points included duration of response, progression-free survival, overall survival, and safety.

Results: As of October 5, 2020, 18 of 90 treated patients (20%) had completed 35 cycles of pembrolizumab and 52 (58%) had discontinued treatment. In the efficacy population (patients who received ≥ 1 dose of pembrolizumab and had ≥ 26 weeks of follow-up; N = 79), the median time from first dose to data cutoff was 42.6 (range, 6.4-56.1) months. The objective response rate was 48% (95% CI, 37 to 60), and median duration of response was not reached (2.9-49.7+ months). Median progression-free survival was 13.1 (95% CI, 4.3 to 34.4) months, and median overall survival was not reached (95% CI, 27.2 months to not reached). Among all treated patients, 76% had ≥ 1 treatment-related adverse event (grades 3-4, 12%). There were no fatal treatment-related events. Immune-mediated adverse events or infusion reactions occurred in 28% of patients (grades 3-4, 7%; no fatal events).

Conclusion: Pembrolizumab demonstrated robust and durable antitumor activity and encouraging survival outcomes with manageable toxicity in patients with previously treated, advanced MSI-H/dMMR endometrial cancer.

FIG 1.

Disposition of patients' study medication status in the safety population (ie, all patients who received ≥ 1 dose of pembrolizumab). ^aIncludes patients with clinical and radiographic progression. ^bTwo patients received a second course of pembrolizumab, one of whom had second course up to cycle 3 and the other had second course up to cycle 12. ^cPatients who received ≥ 1 dose of pembrolizumab and had been enrolled ≥ 26 weeks before data cutoff. AE, adverse event; CR, complete response; dMMR; mismatch repair deficiency; MSI-H, high levels of microsatellite instability.

FIG 2.

(A) Best percentage change from baseline in target lesion size. (B) Time to response and duration of response for patients with a response. (C) Kaplan-Meier analysis of duration of response per RECIST version 1.1. Light blue lines indicate 95% confidence bands. For each figure, all assessments are per RECIST version 1.1 by independent central review. ^aCR was the last overall response before data cutoff and was not confirmed as of the data cutoff date. CR, complete response; NR, not reached; PD, progressive disease; PR, partial response.

FIG 3.

Kaplan-Meier analysis of (A) PFS per RECIST version 1.1 by independent central radiologic review in the efficacy analysis population and (B) OS in the efficacy analysis population. Light blue lines indicate 95% confidence bands. NR, not reached; OS, overall survival; PFS, progression-free survival.