Comparison of survival outcomes between dostarlimab and comparator treatments (tx) in patients (pts) with advanced/recurrent (A/R) endometrial cancer (EC) in England: Matching-adjusted indirect comparisons (MAICs).

Abstract

e17534 Background: Limited tx options exist for pts with A/R EC who progress on/after platinum-based chemotherapy (PBCT). This study compared survival outcomes of pts with A/R mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) EC receiving dostarlimab in Cohort A1 of the single-arm, Phase I GARNET trial, with an equivalent real-world (RW) cohort receiving current tx in England. The primary objective compared second-line (2L) overall survival (OS) between cohorts; a secondary objective was time to tx discontinuation (TTD; proxy for progression-free survival). Methods: An overall-2L-tx RW cohort was established using National Cancer Registration and Analysis Service data. Five tx-specific RW cohorts were identified (tx received at 2L in > 5% of pts) (Table). Clinical outcomes between GARNET and RW cohorts were compared using MAICs. Relevant prognostic variables were used to create 3 matching scenarios (SC): SC1: grade, histology, PBCT number; SC2: histology, PBCT number; SC3: race/ethnicity, stage at diagnosis, histology, prior surgery (MMR/MSI status not considered). OS was time from first dostarlimab dose (GARNET) or 2L RW tx (RW cohorts) to any-cause death; MAIC-adjusted hazard ratios (HR, 95% confidence interval [CI]) were estimated by weighted Cox proportional-hazards models. TTD after MAIC was summarized descriptively. Results: Effective sample size (ESS) assessed matching capacity; lower ESS in SC1 reduced its robustness (Table). Following matching, distributions of baseline characteristics were similar between cohorts. Across most matching scenarios, there was a lower risk of death in pts treated with dostarlimab compared to the overall RW cohort and for tx-specific RW cohorts (Table). Median TTD (months, 95% CI) was longer for pts treated with dostarlimab across all matching scenarios (SC1: 7.8 [4.1, not estimable (NE)]; SC2: 9.7 [5.5, NE]; SC3: 14.0 [6.4, 17.9]) than the overall RW cohort (3.4 [3.2, 3.4]). Conclusions: Results suggest that pts in GARNET with dMMR/MSI-H A/R EC receiving dostarlimab had better OS and longer TTD compared with pts receiving current 2L tx in England. Funding: GSK (217216; scott.r.goulden@gsk.com).[Table: see text]

Outcomes for Dostarlimab and Real-World Treatments in Post-platinum Patients With Advanced/Recurrent Endometrial Cancer: The GARNET Trial Versus a US Electronic Health Record-Based External Control Arm

“…This is consistent with previous analyses showing that dostarlimab-treated patients with advanced or recurrent EC had increased OS when compared with patients treated with the chemotherapy doxorubicin 27 or with patients receiving real-world treatments in England. 28 The longer OS seen with dostarlimab treatment compared with the external control arm could potentially be due to (1) the relatively high response rate seen in GARNET (objective response rate for the dMMR/MSI-H population: 45.5% [95% CI, 37.1%-54.0%]) 29 compared with the relatively low response rates observed with commonly used therapies, 3 and (2) the durability of response seen in GARNET, where Kaplan-Meier analysis indicated a 90.9% chance of maintaining a response at 12 months, a 80.1% chance at 18 months, 21 and an 83.7% chance of remaining in response at 24 months follow-up. 30 Additionally, patients had a long TTD when treated with dostarlimab (9.9 months in the GARNET trial cohort), suggesting a favorable tolerability profile for dostarlimab, enabling patients to remain on treatment.…”

Outcomes for Dostarlimab and Real-World Treatments in Post-platinum Patients With Advanced/Recurrent Endometrial Cancer: The GARNET Trial Versus a US Electronic Health Record-Based External Control Arm

“…This is consistent with previous analyses showing that dostarlimab-treated patients with advanced or recurrent EC had increased OS when compared with patients treated with the chemotherapy doxorubicin 27 or with patients receiving real-world treatments in England. 28 The longer OS seen with dostarlimab treatment compared with the external control arm could potentially be due to (1) the relatively high response rate seen in GARNET (objective response rate for the dMMR/MSI-H population: 45.5% [95% CI, 37.1%-54.0%]) 29 compared with the relatively low response rates observed with commonly used therapies, 3 and (2) the durability of response seen in GARNET, where Kaplan-Meier analysis indicated a 90.9% chance of maintaining a response at 12 months, a 80.1% chance at 18 months, 21 and an 83.7% chance of remaining in response at 24 months follow-up. 30 Additionally, patients had a long TTD when treated with dostarlimab (9.9 months in the GARNET trial cohort), suggesting a favorable tolerability profile for dostarlimab, enabling patients to remain on treatment.…”