Scott Goulden, Qin Shen, Robert Coleman, Cara Mathews, Matthias Hunger, Ankit Pahwa, Rene Schade
{"title":"多斯塔利单抗和真实世界治疗在铂后晚期/复发子宫内膜癌患者中的结果:GARNET试验与基于美国电子健康记录的外部控制臂","authors":"Scott Goulden, Qin Shen, Robert Coleman, Cara Mathews, Matthias Hunger, Ankit Pahwa, Rene Schade","doi":"10.36469/jheor.2023.77484","DOIUrl":null,"url":null,"abstract":"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.","PeriodicalId":16012,"journal":{"name":"Journal of Health Economics and Outcomes Research","volume":"94 1","pages":"0"},"PeriodicalIF":2.3000,"publicationDate":"2023-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"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\",\"authors\":\"Scott Goulden, Qin Shen, Robert Coleman, Cara Mathews, Matthias Hunger, Ankit Pahwa, Rene Schade\",\"doi\":\"10.36469/jheor.2023.77484\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"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.\",\"PeriodicalId\":16012,\"journal\":{\"name\":\"Journal of Health Economics and Outcomes Research\",\"volume\":\"94 1\",\"pages\":\"0\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2023-09-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Health Economics and Outcomes Research\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.36469/jheor.2023.77484\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ECONOMICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Health Economics and Outcomes Research","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.36469/jheor.2023.77484","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ECONOMICS","Score":null,"Total":0}
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 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.