Antitumor activity and safety of dostarlimab therapy in patients with endometrial cancer by age subgroups: A post-hoc analysis from the GARNET trial (210)

Abstract

<b>Objectives:</b> Although the median age of diagnosis of endometrial cancer (EC) is 62 years (y), most deaths from EC occur in patients (pts) older than 65 y (median age at death is 70 y). The current standard of care in EC does not address the unmet need for care in older pts. Dostarlimab is a programmed death receptor 1 (PD-1)-blocking antibody approved in the US for <i>(1)</i> the treatment of adults with mismatch repair deficient (dMMR) recurrent/advanced EC that has progressed on or after prior treatment with a platinum-containing regimen or <i>(2)</i> dMMR recurrent/advanced solid tumors that have progressed on or after prior treatment and who have no satisfactory alternative treatment option. Here, we present a post-hoc analysis of the antitumor activity and safety of dostarlimab by age subgroup in pts with dMMR/microsatellite instability-high (MSI-H) EC and mismatch repair proficient (MMRp)/microsatellite stable (MSS) EC. <b>Methods:</b> GARNET is a phase I, multi-center, open-label, single-arm study of dostarlimab monotherapy in pts with advanced/recurrent solid tumors. Within GARNET, two expansion cohorts enrolled pts with advanced/recurrent EC: cohort A1 enrolled pts with dMMR/ MSI-H EC, and cohort A2 enrolled pts with MMRp/MSS EC. Based on age at baseline, pts were stratified into three age groups: <65 y, ≥65 to <75 y, and ≥75 y. Antitumor activity and safety were assessed in each subgroup by using data from the March 1, 2020, interim analysis. <b>Results:</b> Of 129 pts with dMMR/MSI-H EC enrolled in cohort A1, 51.2% (<i>n</i>=66) were <65 y, 39.5% (<i>n</i>=51) were ≥65 to <75 y, and 9.3% (<i>n</i>=12) were ≥75 y. Of 161 pts with MMRp/MSS EC enrolled in cohort A2, 43.5% (<i>n</i>=70) were <65 y, 44.7% (<i>n</i>=72) were ≥65 to <75 y, and 11.8% (<i>n</i>=19) were ≥75 y. For this interim analysis, pts with measurable disease at baseline and sufficient follow-up time (≥24 weeks) were included in the efficacy-evaluable population. The confirmed objective response rates (ORRs) per RECIST v1.1 assessed by blinded independent central review were similar across age groups for dMMR/MSI-H EC (<65 y: 45.3%; 95% CI: 31.6%-59.6%; ≥65 to <75 y: 43.9%; 95% CI: 28.5%-60.3%; ≥75 y: 45.5%; 95% CI: 16.7%-76.6%). The confirmed ORRs for pts with MMRp/MSS EC were not dissimilar across age groups (<65 y: 9.1%; 95% CI: 3.4%-18.7%; ≥65 to <75 y: 16.9%; 95% CI: 9.0%-27.7%; ≥75 y: 21.1%; 95% CI: 6.1%-45.6%). There were few grade ≥3 treatment-related adverse events (TRAEs) and these were generally similar between age groups. Pts aged ≥75 y did not have increased incidence of grade ≥3 TRAEs compared with younger age groups (Table). <b>Conclusions:</b> Dostarlimab's antitumor activity and safety for pts with dMMR/MSI-H EC and MMRp/MSS EC were generally comparable across age groups, with low incidence of grade ≥3 TRAEs across all subgroups. Older pts with advanced/recurrent dMMR/MSI-H EC experienced broadly similar treatment benefits as younger pts.