2 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. A summary of the article by Guilhem Roubaud, Gerhardt Attard, Martin Boegemann, David Olmos, Marco Trevisan, Laurent Antoni, Katie Pascoe, Camille Capone, Suzy Van Sandeng, Mahmoud Hashim, Stephen Palmeri, Kim Chi published in the European Journal of Cancer 209 (2024) 114183 Study Background and Objectives · The MAGNITUDE study aimed to assess the clinical benets of niraparib in combination with abiraterone acetate plus prednisone compared to placebo plus abiraterone acetate in patients with BRCA1/2-altered mCRPC. · Initial analyses indicated imbalances in baseline characteristics between treatment arms, which could affect the estimation of clinical benets and costeffectiveness. In particular, a higher proportion of patients at baseline in the niraparib+ abiraterone acetate plus prednisone (+AAP) arm had poor prognostic features versus abiraterone acetate plus prednisone (+AAP) which may have disadvantaged outcomes in this treatment group. · This analysis utilized inverse probability of treatment weighting (IPTW) to adjust for these imbalances and evaluate time-toevent outcomes. Methods Magnitude Study design The original MAGNITUDE STUDY was a phase 3, double-blind, placebo-controlled, Multicentre study in patients with mCRPC with (Cohort 1) and without (Cohort 2) alterations in HRR-associated genes (ATM, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, HDAC2, PALB2). The primary endpoint was radiographic progression survival (rPFS), dened as the time from randomisation to date of radiographic progression or death, whichever occurred rst, as assessed by blinded independent central review (BICR). The post hoc Analysis – The Inverse probability of treatment weighting Analysis Study In this post hoc IPTW analysis was performed on 225 patients with BRCA1/2-altered mCRPC to adjust for baseline imbalances on treatment effects. Outcomes were compared between those receiving niraparib plus abiraterone acetate plus prednisone and those receiving placebo plus abiraterone acetate plus prednisone. · Key outcomes assessed included: § overall survival (OS) § radiographic progression-free survival (rPFS) § time to symptomatic progression (TSP) § time to initiation of cytotoxic chemotherapy (TCC) § time to prostate-specic antigen (PSA) progression. · Weighted Kaplan-Meier curves and adjusted hazard ratios (HR) were generated to analyze the data. Results · Overall Survival: o Unadjusted median OS was 30.4 months for niraparib plus AAP versus 28.6 months for placebo plus AAP (HR: 0.79; p = 0.183). o After IPTW adjustment, median OS improved to 34.1 months for niraparib plus AAP and decreased to 27.4 months for placebo (HR: 0.65; p = 0.017), indicating a 35% reduction in the risk of death.
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