GlaxoSmithKline, London, United Kingdom
Scott Goulden , Kiera Heffernan , Fulya Sen Nikitas , Urmi Shukla , Craig Knott , Matthias Hunger , Ankit Pahwa , Rene Schade
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).
HR for OS (dostarlimab vs) (95% CI) [ESS] | SC1 | SC2 | SC3 |
---|---|---|---|
Overall | 0.52 (0.29, 0.92) [34]* | 0.35 (0.22, 0.55) [74]* | 0.31 (0.20, 0.49) [75]* |
Paclitaxel mono | 0.36 (0.19, 0.65) [30]* | 0.24 (0.15, 0.40) [72]* | 0.18 (0.11, 0.30) [63]* |
Carboplatin+paclitaxel | 0.70 (0.39, 1.28) [36] | 0.48 (0.29, 0.78) [74]* | 0.42 (0.25, 0.68) [69]* |
Carboplatin+dox | 0.74 (0.39, 1.41) [26] | 0.45 (0.27, 0.76) [69]* | 0.40 (0.24, 0.67) [74]* |
Dox mono | 0.20 (0.09, 0.44) [37]* | 0.17 (0.10, 0.29) [78]* | 0.16 (0.09, 0.27) [76]* |
Carboplatin mono | 0.53 (0.29, 0.98) [23]* | 0.32 (0.19, 0.55) [67]* | 0.28 (0.16, 0.48) [69]* |
Dox, liposomal doxorubicin; mono, monotherapy; *P< 0.05
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