The comparative clinical effectiveness of dostarlimab versus doxorubicin in the treatment of advanced/recurrent endometrial cancer

Objectives: Patients (pts) with advanced/recurrent (A/R) endometrial cancer (EC) have limited treatment (tx) options following platinum therapy. Dostarlimab (JEMPERLI) is approved for pts with A/R mismatch repair-deficient/microsatellite instability-high (dMMR/ MSI-H) EC. Dostarlimab efficacy versus other tx options was not evaluated in the single-arm GARNET study (NCT02715284). A systematic literature review identified ZoptEC (NCT01767155), in which pts with A/R EC received AEZS-108 (zoptarelin doxorubicin [dox]) or dox alone, as a relevant trial for indirect treatment comparison (ITC) versus GARNET. This ITC aimed to describe the efficacy and safety of dostarlimab versus dox using inverse probability of treatment weighting (IPTW) methodology. Methods: Pt-level data and study variables were merged from GARNET Cohort A1 (dMMR/MSI-H EC) and the ZoptEC dox control arm (dMMR/MSI-H status not collected). Pts were matched based on eligibility criteria for the main analysis population. Sensitivity analysis included all pts who received study drugs in GARNET Cohort A1 and the ZoptEC dox arm (safety population). For overall survival (OS), a Cox proportional hazards model with IPTW (a multi-step estimation procedure to control for confounding variables) was used. Kaplan-Meier analysis was used for progression-free survival (PFS), duration of response (DoR), and time to deterioration (TTD) in quality of life (QOL). Descriptive analyses were used for overall response rate (ORR), treatment-emergent adverse events (AEs), serious AEs (SAEs), and Grade ≥3 AEs. The Clopper-Pearson method was used for 95% CI estimates. Conclusions: In this ITC of GARNET A1 and ZoptEC, improved OS was observed with dostarlimab versus dox in pts with A/R EC. Dostarlimab and dox safety profiles were consistent with prior studies. Despite inherent limitations of ITC and IPTW analyses, differences in pt numbers, and biomarker status in the two trials, this study suggests dostarlimab has a favorable benefit-risk ratio in pts with A/R EC. Funding: GSK (215333). Editorial support provided by Fishawack Indicia, part of Fishawack Health, funded by GSK. Acknowledgments: Data were made under license from Aeterna Zentaris. Objectives: Patients (pts) with advanced/recurrent (A/R) endometrial cancer (EC) have limited treatment (tx) options following platinum therapy. Dostarlimab (JEMPERLI) is approved for pts with A/R mismatch repair-deficient/microsatellite instability-high (dMMR/ MSI-H) EC. Dostarlimab efficacy versus other tx options was not evaluated in the single-arm GARNET study (NCT02715284). A systematic literature review identified ZoptEC (NCT01767155), in which pts with A/R EC received AEZS-108 (zoptarelin doxorubicin [dox]) or dox alone, as a relevant trial for indirect treatment comparison (ITC) versus GARNET. This ITC aimed to describe the efficacy and safety of dostarlimab versus dox using inverse probability of treatment weighting (IPTW) methodology. Methods: Pt-level data and study variables were merged from GARNET Cohort A1 (dMMR/MSI-H EC) and the ZoptEC dox control arm (dMMR/MSI-H status not collected). Pts were matched based on eligibility criteria for the main analysis population. Sensitivity analysis included all pts who received study drugs in GARNET Cohort A1 and the ZoptEC dox arm (safety population). For overall survival (OS), a Cox proportional hazards model with IPTW (a multi-step estimation procedure to control for confounding variables) was used. Kaplan-Meier analysis was used for progression-free survival (PFS), duration of response (DoR), and time to deterioration (TTD) in quality of life (QOL). Descriptive analyses were used for overall response rate (ORR), treatment-emergent adverse events (AEs), serious AEs (SAEs), and Grade ≥3 AEs. The Clopper-Pearson method was used for 95% CI estimates. Conclusions: In this ITC of GARNET A1 and ZoptEC, improved OS was observed with dostarlimab versus dox in pts with A/R EC. Dostarlimab and dox safety profiles were consistent with prior studies. Despite inherent limitations of ITC and IPTW analyses, differences in pt numbers, and biomarker status in the two trials, this study suggests dostarlimab has a favorable benefit-risk ratio in pts with A/R EC. Funding: GSK (215333). Editorial support provided by Fishawack Indicia, part of Fishawack Health, funded by GSK. Acknowledgments: Data were made under license from Aeterna Zentaris.