Adjustment for imbalances in baseline characteristics in the MAGNITUDE phase 3 study confirms the clinical benefit of niraparib in combination with abiraterone acetate plus prednisone in patients with metastatic prostate cancer.
Eur J Cancer
; 209: 114183, 2024 Sep.
Article
em En
| MEDLINE
| ID: mdl-39111209
ABSTRACT
BACKGROUND:
MAGNITUDE (NCT03748641) demonstrated favourable outcomes with niraparib plus abiraterone acetate plus prednisone (+AAP) versus placebo+AAP in patients with BRCA1/2-altered metastatic castration-resistant prostate cancer (mCRPC). Imbalances in prognostic variables were reported between arms, which impacts estimation of both the clinical benefit and costeffectiveness of niraparib+AAP for healthcare systems. A pre-specified multivariable analysis (MVA) demonstrated improved overall survival (OS) with niraparib+AAP. Here, we used an inverse probability of treatment weighting (IPTW) model to adjust for covariate imbalances and assess time-to-event outcomes.METHODS:
IPTW analysis of time-to-event outcomes was conducted using data from patients with BRCA1/2-altered mCRPC (N = 225) in MAGNITUDE. Patients received niraparib+AAP or placebo+AAP. OS, radiographic progression-free survival, time to symptomatic progression, time to initiation of cytotoxic chemotherapy and time to prostate-specific antigen progression were assessed. Weighted Kaplan-Meier curves were generated for each endpoint, and adjusted hazard ratios (HR) were obtained from a weighted Cox model.RESULTS:
Improvements in survival outcomes were estimated for niraparib+AAP versus placebo+AAP unadjusted median OS was 30.4 months versus 28.6 months, respectively (HR 0.79; 95 % confidence interval [CI] 0.55, 1.12; p = 0.183). Following IPTW, median OS increased to 34.1 months with niraparib+AAP versus a decrease to 27.4 with placebo (HR 0.65; 95 % CI 0.46, 0.93; p = 0.017). Similar improvements were observed for other time-to-event endpoints.CONCLUSIONS:
IPTW adjustment provided a more precise estimate of the clinical benefit of niraparib+AAP versus placebo+AAP in patients with BRCA1/2-altered mCRPC. Results were consistent with the pre-specified MVA, and further demonstrated the value of adjusting for baseline imbalances, particularly in smaller studies. TRIAL REGISTRATION NCT03748641 (MAGNITUDE).Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piperidinas
/
Prednisona
/
Protocolos de Quimioterapia Combinada Antineoplásica
/
Neoplasias de Próstata Resistentes à Castração
/
Acetato de Abiraterona
/
Indazóis
Limite:
Aged
/
Aged80
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Eur J Cancer
Ano de publicação:
2024
Tipo de documento:
Article
País de publicação:
Reino Unido