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

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.