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 cost‑effectiveness 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.
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.
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.
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.
NCT03748641 (MAGNITUDE).
European journal of cancer (Oxford, England : 1990). 2024 Jun 17 [Epub ahead of print]
Guilhem Roubaud, Gerhardt Attard, Martin Boegemann, David Olmos, Marco Trevisan, Laurent Antoni, Katie Pascoe, Camille Capone, Suzy Van Sanden, Mahmoud Hashim, Stephen Palmer, Kim Chi
Department of Medical Oncology, Institut Bergonié, Bordeaux, France. Electronic address: ., University College London Cancer Institute, London, UK., Department of Urology, Muenster University Hospital, Muenster, Germany; Westgerman Cancer Center, Münster, Germany., Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre, Madrid, Spain., Janssen EMEA, Geneva, Switzerland., Janssen Pharmaceutica NV, Beerse, Antwerp, Belgium., Janssen Vaccines & Prevention B.V., Leiden, the Netherlands., Centre for Health Economics, University of York, York, UK., BC Cancer and Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada.