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.

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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). Patients received pembrolizumab 200mg Q3W for ≥35cycles. 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. 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. 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.