Progression-free survival (PFS) and overall survival (OS) in advanced/recurrent (AR) mismatch repair deficient/microsatellite instability-high or proficient/stable (dMMR/MSI-H or MMRp/MSS) endometrial cancer (EC) treated with dostarlimab in the GARNET study

Dostarlimab is a programmed death 1 (PD-1) inhibitor approved in the EU as a monotherapy in patients (pts) with dMMR/MSI-H AR EC that has progressed on or after platinum-based chemotherapy; and in the US as a monotherapy in pts with dMMR AR EC that has progressed on or after platinum-based chemotherapy or dMMR solid tumors that have progressed on or after prior treatment, with no satisfactory alternative treatment options. We report on PFS and OS in 2 expansion cohorts of the GARNET trial that enrolled pts with EC. GARNET is a multicenter, open-label, single-arm phase 1 study. Pts were assigned to cohort A1 (dMMR/MSI-H EC) or A2 (MMRp/MSS EC) based on local immunohistochemistry assessment. Pts received 500 mg of dostarlimab IV every 3 weeks for 4 cycles, then 1000 mg every 6 weeks until disease progression, discontinuation, or withdrawal. PFS and OS are secondary efficacy endpoints. 153 pts with dMMR/MSI-H and 161 pts with MMRp/MSS EC were enrolled and treated. The efficacy-evaluable population included 143 pts with dMMR/MSI-H EC and 156 pts with MMRp/MSS EC with measurable disease at baseline and ≥6 mo of follow-up. Median follow-up was 27.6 mo for dMMR/MSI-H and 33.0 mo for MMRp/MSS EC (Table). For pts with dMMR/MSI-H EC, median PFS (mPFS) was 6.0 mo, with 3-year estimated PFS rate of 40.1%. With 37.3% of pts experiencing an event, mOS was not reached; estimated 3-year OS was >50%. For pts with MMRp/MSS EC, mPFS was 2.7 mo. mOS was 16.9 mo with 68.9% of pts experiencing an event. Safety has been previously reported.Table: 548PdMMR/MSI-H ECN=143MMRp/MSS ECN=156Median follow-up, mo27.633.0mPFS (95% CI), mo6.0 (4.1–18.0)2.7 (2.6–2.8)Estimated probability of PFS, %12 mo24 mo36 mo46.440.140.113.39.46.8N=153N=161mOS (95% CI), moNR (25.7–NR)16.9 (13.0–21.8)Estimated probability of survival, %12 mo24 mo36 mo73.360.558.460.638.422.2Datacut: 1 Nov 2021. NR, not reached Open table in a new tab Datacut: 1 Nov 2021. NR, not reached Dostarlimab demonstrated durable antitumor activity in dMMR/MSI-H and MMRp/MSS AR EC. dMMR/MSI-H was associated with longer PFS and OS than MMRp/MSS as expected.