Background The potential benefits of immunotherapy following discontinuation for reasons other than progressive disease (PD) are not well described. Furthermore, some patients may benefit from remaining on immunotherapy beyond 2 years. We evaluated ORR and DOR in subgroups of patients with endometrial cancer (EC) per reason for treatment discontinuation and duration of treatment ≥2 years.

Methods GARNET is a multicenter, open-label, single-arm phase 1 study. Patients were assigned to cohort A1 (mismatch repair deficient [dMMR]/microsatellite instability–high [MSI-H] EC) or A2 (MMR proficient [MMRp]/microsatellite stable [MSS] EC) based on immunohistochemistry assessment. Patients received 500 mg of dostarlimab IV Q3W for 4 cycles, then 1000 mg Q6W until PD, discontinuation, or withdrawal; treatment could be considered beyond 2 years following discussion between sponsor and investigator. Primary endpoints were ORR, DOR, and safety. Subgroups in this post hoc analysis were thus: patients who discontinued treatment due to PD, those who discontinued for reasons other than PD, patients who remained on treatment for ≥2 years, and patients who discontinued before 2 years.

Results 299 patients with dMMR and MMRp EC were included in the efficacy-evaluable population. 88 patients discontinued for reasons other than PD, 164 discontinued for PD, and 47 remain on treatment (table 1). The median duration of follow-up was 27.7 months, and median DOR (mDOR) was not reached (NR) for patients who discontinued for reasons other than PD; 75% (18/24) of responders remain in response. mDOR was 9.8 months for patients discontinuing due to PD and was NR for those who remain on treatment; 90.9% (40/44) of responders who remain on treatment remain in response.

Nearly 52% of patients with complete response, partial response (PR), or stable disease (SD) remained on treatment for ≥2 years (46 of 89 responders). Of those patients who were on treatment for ≥2 years, 59.6% had PR and 8.5% had SD as their best response. 25% of patients (12/47) who remained on treatment for ≥2 years had MMRp/MSS tumors.

Safety has been previously reported.1

Conclusions Patients demonstrated durable responses to treatment when they discontinued for reasons other than PD. Meaningful durability (≥2 years) was observed even in patients with SD and PR. Biomarkers of durable responses to immunotherapy are needed.

Trial Registration NCT02715284

Reference

1. Oaknin A, Pothuri B, Gilbert L, et al. Dostarlimab in advanced/recurrent (AR) mismatch repair deficient/microsatellite instability-high or proficient/stable (dMMR/MSI-H or MMRp/MSS) endometrial cancer (EC): The GARNET study. J Clin Oncol. 2022;40(16_suppl):5509–5509.

Ethics Approval This study was approved by Western Institutional Review Board, #20160056.