Pembrolizumab in microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) and non-MSI-H/non-dMMR advanced endometrial cancer: Phase 2 KEYNOTE-158 study results
- Author(s)
- O'Malley, DM; Bariani, GM; Cassier, PA; Marabelle, A; Hansen, AR; Acosta, AJ; Miller, WH, Jr; Safra, T; Italiano, A; Mileshkin, L; Yao, L; Gozman, A; Jin, F; Maio, M;
- Journal Title
- Gynecologic Oncology
- Publication Type
- Online publication before print
- Abstract
- OBJECTIVE: We report updated results with longer follow-up in patients with MSI-H/dMMR endometrial cancer (EC) in cohort D (advanced EC of any MSI/dMMR status) and cohort K (any MSI-H/dMMR advanced solid tumor, except colorectal) of the phase 2 KEYNOTE-158 study (NCT02628067) and the first results from patients with non-MSI-H/non-dMMR advanced EC (cohort D). METHODS: Patients received pembrolizumab 200 mg Q3W for ≥35 cycles. The primary endpoint was objective response rate (ORR) per RECIST v1.1 by central review. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: As of January 12, 2022, median (range) follow-up in the MSI-H/dMMR (n = 94) and non-MSI-H/non-dMMR (n = 96) groups was 54.5 (14.7-71.4) and 68.3 (64.3-71.9) months, respectively. The ORR (95 % CI) was 50 % (40 %-61 %) in the MSI-H/dMMR group; 15 patients (16 %) experienced a complete response, 32 (34 %) experienced a partial response. The ORR (95 % CI) in the non-MSI-H/non-dMMR group was 7 % (3 %-14 %); 7 patients (7 %) experienced a partial response, none experienced a complete response. The estimated 4-year DOR rates were 66 % and 56 %, respectively. Median PFS was 13.1 (95 % CI, 4.3-25.7) months in the MSI-H/dMMR group and 2.1 (95 % CI, 2.1-2.2) months in the non-MSI-H/non-dMMR group. Median OS was 65.4 (95 % CI, 29.5-not reached) and 11.1 (95 % CI, 8.1-15.3) months, respectively. Toxicity was manageable in both groups. CONCLUSIONS: These results continue to support pembrolizumab as a standard-of-care option for MSI-H/dMMR advanced EC in patients with disease progression following prior systemic therapy who are not candidates for curative surgery or radiation.
- Keywords
- Advanced endometrial cancer; DNA mismatch repair deficiency; Microsatellite instability-high; Pembrolizumab
- Department(s)
- Medical Oncology
- Publisher's Version
- https://doi.org/10.1016/j.ygyno.2024.12.020
- Open Access at Publisher's Site
https://doi.org/10.1016/j.ygyno.2024.12.020- Terms of Use/Rights Notice
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Creation Date: 2025-01-30 02:31:34
Last Modified: 2025-01-30 02:34:12