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.

Autor: Roubaud G; Department of Medical Oncology, Institut Bergonié, Bordeaux, France. Electronic address: g.roubaud@bordeaux.unicancer.fr., Attard G; University College London Cancer Institute, London, UK., Boegemann M; Department of Urology, Muenster University Hospital, Muenster, Germany; Westgerman Cancer Center, Münster, Germany., Olmos D; Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre, Madrid, Spain., Trevisan M; Janssen EMEA, Geneva, Switzerland., Antoni L; Janssen Pharmaceutica NV, Beerse, Antwerp, Belgium., Pascoe K; Janssen Vaccines & Prevention B.V., Leiden, the Netherlands., Capone C; Janssen Pharmaceutica NV, Beerse, Antwerp, Belgium., Van Sanden S; Janssen Pharmaceutica NV, Beerse, Antwerp, Belgium., Hashim M; Janssen Vaccines & Prevention B.V., Leiden, the Netherlands., Palmer S; Centre for Health Economics, University of York, York, UK., Chi K; BC Cancer and Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada.
Jazyk: angličtina
Zdroj: European journal of cancer (Oxford, England : 1990) [Eur J Cancer] 2024 Sep; Vol. 209, pp. 114183. Date of Electronic Publication: 2024 Jun 17.
DOI: 10.1016/j.ejca.2024.114183
Abstrakt: 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 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.
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).
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: GR: Received consulting or advisory role fees from Astellas, AstraZeneca, Janssen, Merck and Pfizer; research funding from Bayer; and travel, accommodations, or expense reimbursements from Janssen. GA: Received honoraria from Astellas and Janssen; consulting or advisory fees from Abbott Laboratories, Astellas, AstraZeneca, Bayer, ESSA, Ferring, Janssen, Medivation, Millennium, Novartis, Pfizer, Ventana Medical Systems and Veridex; speakers’ bureau fees from Astellas, AstraZeneca, Ferring, Ipsen, Janssen, Sanofi, Takeda and Ventana Medical Systems; research funding from Arno Therapeutics, Innocrin Pharma and Janssen; has patents or other intellectual property or received royalties for abiraterone acetate; received travel, accommodations, or expense reimbursements from Abbott Laboratories, Astellas, Bayer, ESSA, Ferring, Janssen, Medivation, Pfizer and Ventana Medical Systems; and is affiliated with the Institute of Cancer Research. MB: Received honoraria from Advanced Accelerator Applications, Amgen, Astellas, AstraZeneca, Bayer/Vital, Bristol Myers Squibb, Eisai, EUSA Pharma, Ipsen, Janssen, Merck, MSD, Novartis, Pfizer, Roche, and Sanofi/Aventis; consulting or advisory role for Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, Ipsen, Janssen, Merck, MSD, Novartis, Roche, and Sanofi; institution received research funding from Ipsen and Janssen; received travel, accommodation and expenses from Amgen, Bayer, Bristol Myers Squibb, and Janssen; employment at Janssen. DO: Received honoraria from Astellas, Bayer and Janssen; consulting or advisory role fees from AstraZeneca, Bayer, Clovis Oncology, Daiichi Sankyo, Janssen and Merck; research funding from Astellas, AstraZeneca, Bayer, Genentech/Roche, Janssen, Medivation, Merck, Pfizer and Tokai Pharmaceuticals; and travel, accommodations, or expense reimbursements from Astellas, AstraZeneca, Bayer, Ipsen, Janssen and Roche. KP: Employee of Janssen and shareholder of Johnson and Johnson. MT, LA, CC, SVS, MH: Employees of Janssen. SP: Received consultancy fees from Janssen for participation in advisory boards and general methodological advice. KC: Received honoraria from Astellas, AstraZeneca, Bayer, Janssen, Merck, and Roche; consulting or advisory fees from Amgen, Astellas, AstraZeneca, Bayer, Constellation Pharmaceuticals, Daiichi Sankyo, ESSA, Janssen, Merck, POINT Biopharma, Roche, and Sanofi; research funding from Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, ESSA, Janssen, Merck, Novartis, Pfizer, Roche, and Sanofi; and gave expert testimony for AstraZeneca and Novartis.
(Copyright © 2024. Published by Elsevier Ltd.)
Databáze: MEDLINE
Externí odkaz: