546P Pembrolizumab for microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) advanced endometrial cancer: Long-term follow-up results from KEYNOTE-158

Abstract

Pembrolizumab (pembro) previously demonstrated robust and durable antitumor activity in patients with MSI-H/dMMR advanced endometrial cancer in the open-label, multicohort, phase 2 KEYNOTE-158 study (NCT02628067). Here we report updated efficacy and safety outcomes with a substantially longer follow-up in the patients enrolled. This analysis included those patients with previously treated, MSI-H/dMMR advanced endometrial cancer enrolled in cohorts D (advanced endometrial cancer of any MSI/MMR status) and K (any MSI-H/dMMR advanced solid tumor, except colorectal) of KEYNOTE-158. MSI-H/dMMR status was determined retrospectively by PCR at a central lab in cohort D and prospectively by PCR and/or IHC at a local lab in cohort K. Patients received pembro 200 mg Q3W for up to 35 cycles. Primary endpoint was ORR per RECIST v1.1 by independent central radiologic review. Secondary endpoints included DOR, PFS, OS, and safety. 94 patients with previously treated MSI-H/dMMR advanced endometrial cancer were included in this analysis. Median time from first dose to data cutoff (Jan 12, 2022) was 54.5 (range, 14.7–71.4) mo. Efficacy results are shown in the Table. ORR was 50% (95% CI, 39.5%–60.5%); responses were seen across all prior treatment lines. 4-y DOR rate was 66% by K-M estimate. Median (95% CI) PFS and OS were 13.1 (4.3‒25.7) mo and 65.4 (29.5‒NR) mo; 4-y PFS and OS rates were 37% and 59%, respectively. Treatment-related AEs occurred in 71 patients (76%); 13 patients (14%) had grade 3‒4 treatment-related AEs (no grade 5).Table: 546PAnalysis population (n = 94)ORR, % (95% CI)50 (39.5–60.5) CR, n (%)15 (16) PR, n (%)32 (34) SD, n (%)17 (18)ORR by prior treatment line, % (95% CI)a Neo-adjuvant and/or adjuvant therapy only (n = 10)40 (12.2–73.8) 1 line (n = 39)59 (42.1–74.4) >1 line (n = 45)44 (29.6–60.0)DOR, median (range),b mo63.2 (2.9–63.2) DOR ≥1 y,b %87 DOR ≥2 y,b %71 DOR ≥3 y,b %66 DOR ≥4 y,b %66Median PFS (95% CI),b mo13.1 (4.3–25.7) 4-y PFS rate,b %37Median OS (95% CI),b mo65.4 (29.5–NR) 4-y OS rate,b %59K-M, Kaplan-Meier; NR, not reached. aPercentages are based on number of patients in each subgroup. bK-M estimate Open table in a new tab K-M, Kaplan-Meier; NR, not reached. aPercentages are based on number of patients in each subgroup. bK-M estimate These updated results reconfirm the robust and durable antitumor activity of pembro and show encouraging survival outcomes in patients with advanced endometrial carcinoma that is MSI-H/dMMR, who have PD following prior systemic therapy and are not candidates for curative surgery or radiation, supporting the use of pembro in this setting.