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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

Background: Patients with advanced or recurrent endometrial cancer (EC) have limited treatment options following platinum-based chemotherapy and poor prognosis. The single-arm, Phase I GARNET trial (NCT02715284) previously reported dostarlimab efficacy in mismatch repair–deficient/microsatellite ins...

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Autores principales: Goulden, Scott, Shen, Qin, Coleman, Robert L., Mathews, Cara, Hunger, Matthias, Pahwa, Ankit, Schade, Rene
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Columbia Data Analytics, LLC 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10493167/
https://www.ncbi.nlm.nih.gov/pubmed/37701519
http://dx.doi.org/10.36469/001c.77484
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author Goulden, Scott
Shen, Qin
Coleman, Robert L.
Mathews, Cara
Hunger, Matthias
Pahwa, Ankit
Schade, Rene
author_facet Goulden, Scott
Shen, Qin
Coleman, Robert L.
Mathews, Cara
Hunger, Matthias
Pahwa, Ankit
Schade, Rene
author_sort Goulden, Scott
collection PubMed
description Background: Patients with advanced or recurrent endometrial cancer (EC) have limited treatment options following platinum-based chemotherapy and poor prognosis. The single-arm, Phase I GARNET trial (NCT02715284) previously reported dostarlimab efficacy in mismatch repair–deficient/microsatellite instability–high advanced or recurrent EC. Objectives: The objective of this study was to compare overall survival (OS) and describe time to treatment discontinuation (TTD) for dostarlimab (GARNET Cohort A1 safety population) with an equivalent real-world external control arm receiving non-anti-programmed death (PD)-1/PD-ligand (L)1/2 treatments (constructed using data from a nationwide electronic health record–derived de-identified database and applied GARNET eligibility criteria). Methods: Propensity scores constructed from prognostic factors, identified by literature review and clinical experts, were used for inverse probability of treatment weighting (IPTW). Kaplan-Meier curves were constructed and OS/TTD was estimated (Cox regression model was used to estimate the OS-adjusted hazard ratio). Results: Dostarlimab was associated with a 52% lower risk of death vs real-world treatments (hazard ratio, 0.48; 95% confidence interval [CI], 0.35-0.66). IPTW-adjusted median OS for dostarlimab (N=143) was not estimable (95% CI, 19.4–not estimable) versus 13.1 months (95% CI, 8.3-15.9) for real-world treatments (N = 185). Median TTD was 11.7 months (95% CI, 6.0-38.7) for dostarlimab and 5.3 months (95% CI, 4.1-6.0) for the real-world cohort. Discussion: Consistent with previous analyses, patients treated with dostarlimab had significantly longer OS than patients in the US real-world cohort after adjusting for the lack of randomization using stabilized IPTW. Additionally, patients had a long TTD when treated with dostarlimab, suggesting a favorable tolerability profile. Conclusion: Patients with advanced or recurrent EC receiving dostarlimab in GARNET had significantly lower risk of death than those receiving real-world non-anti-PD-(L)1/2 treatments.
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spelling pubmed-104931672023-09-11 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 Goulden, Scott Shen, Qin Coleman, Robert L. Mathews, Cara Hunger, Matthias Pahwa, Ankit Schade, Rene J Health Econ Outcomes Res Oncology Background: Patients with advanced or recurrent endometrial cancer (EC) have limited treatment options following platinum-based chemotherapy and poor prognosis. The single-arm, Phase I GARNET trial (NCT02715284) previously reported dostarlimab efficacy in mismatch repair–deficient/microsatellite instability–high advanced or recurrent EC. Objectives: The objective of this study was to compare overall survival (OS) and describe time to treatment discontinuation (TTD) for dostarlimab (GARNET Cohort A1 safety population) with an equivalent real-world external control arm receiving non-anti-programmed death (PD)-1/PD-ligand (L)1/2 treatments (constructed using data from a nationwide electronic health record–derived de-identified database and applied GARNET eligibility criteria). Methods: Propensity scores constructed from prognostic factors, identified by literature review and clinical experts, were used for inverse probability of treatment weighting (IPTW). Kaplan-Meier curves were constructed and OS/TTD was estimated (Cox regression model was used to estimate the OS-adjusted hazard ratio). Results: Dostarlimab was associated with a 52% lower risk of death vs real-world treatments (hazard ratio, 0.48; 95% confidence interval [CI], 0.35-0.66). IPTW-adjusted median OS for dostarlimab (N=143) was not estimable (95% CI, 19.4–not estimable) versus 13.1 months (95% CI, 8.3-15.9) for real-world treatments (N = 185). Median TTD was 11.7 months (95% CI, 6.0-38.7) for dostarlimab and 5.3 months (95% CI, 4.1-6.0) for the real-world cohort. Discussion: Consistent with previous analyses, patients treated with dostarlimab had significantly longer OS than patients in the US real-world cohort after adjusting for the lack of randomization using stabilized IPTW. Additionally, patients had a long TTD when treated with dostarlimab, suggesting a favorable tolerability profile. Conclusion: Patients with advanced or recurrent EC receiving dostarlimab in GARNET had significantly lower risk of death than those receiving real-world non-anti-PD-(L)1/2 treatments. Columbia Data Analytics, LLC 2023-09-08 /pmc/articles/PMC10493167/ /pubmed/37701519 http://dx.doi.org/10.36469/001c.77484 Text en https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (4.0) (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Oncology
Goulden, Scott
Shen, Qin
Coleman, Robert L.
Mathews, Cara
Hunger, Matthias
Pahwa, Ankit
Schade, Rene
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10493167/
https://www.ncbi.nlm.nih.gov/pubmed/37701519
http://dx.doi.org/10.36469/001c.77484
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