(UroToday.com) The 2023 ESMO annual meeting included a session on prostate cancer, featuring a presentation by Dr. Gerhardt Attard discussing the efficacy of niraparib and abiraterone acetate + prednisone in HRR gene-altered metastatic castration-resistant prostate cancer (mCRPC) by tissue and/or plasma assays in the MAGNITUDE trial.1
Metastatic castration-resistant prostate cancer with gene alterations in HRR-associated genes has a very poor prognosis. The randomized, double-blind, phase 3 MAGNITUDE study evaluated niraparib + abiraterone acetate + prednisone or placebo + abiraterone acetate + prednisone as first line therapy for mCRPC that was HRR+ based on targeted next-generation sequencing of tumor tissue and/or plasma-based assays.2 At the 2023 ESMO annual congress, Dr. Attard and colleagues assessed treatment efficacy by assay.
Tumor and/or plasma was collected from mCRPC patients who consented to the pre-screening protocol and tested using local tissue assays or centrally using the Foundation Medicine FoundationOne®CDx (F1CDX) tissue assay or Agilent-Resolution Bioscience Resolution HRD™ Plasma (Resolution ctDx plasma) assay. Patients that were HRR+ (BRCA1, BRCA2, FANCA, PALB2, CHEK2, BRIP1, HDAC2, ATM, CDK12) were randomized 1:1 to receive niraparib + abiraterone acetate + prednisone or placebo + abiraterone acetate + prednisone. The primary outcome was radiographic progression-free survival (rPFS), and the secondary end-points were time to cytotoxic chemotherapy, time to symptomatic progression, and overall survival (OS). These outcomes were reported for interim analysis 2 for each subgroup.
Overall, there were 423 patients that were HRR+ with 225 BRCA+ patients. Demographics and baseline clinical disease characteristics were broadly comparable across both assay and biomarker (HRR and BRCA1/2) groups, however, imbalance of prognostic factors disfavoring niraparib + abiraterone acetate + prednisone was noted. As follows is a summary of MAGNITUDE enrollment with F1CDX tissue assay and Resolution ctDx plasma assay:
rPFS, time to cytotoxic chemotherapy, time to symptomatic progression, and OS in all HRR+ patients treated with niraparib + abiraterone acetate + prednisone was comparable for the Resolution ctDx plasma assay and the F1CDX tissue assay:
Similarly, rPFS, time to cytotoxic chemotherapy, time to symptomatic progression, and OS in the BRCA1/2 subgroup of patients treated with niraparib + abiraterone acetate + prednisone was comparable for the Resolution ctDx plasma assay and the F1CDX tissue assay:
Dr. Attard concluded his presentation discussing the efficacy of niraparib and abiraterone acetate + prednisone in HRR gene-altered mCRPC by tissue and/or plasma assays in the MAGNITUDE trial with the following concluding statements:
- Patients with HRR+ mutations identified by either the Resolution ctDx plasma assay or the F1CDx tissue assay demonstrated comparable outcomes for patients treated with niraparib + abiraterone acetate + prednisone
- Clinically meaningful benefit from niraparib + abiraterone acetate + prednisone was similar for BRCA positive patients detected by either tissue or plasma-based assays
- These findings suggest that both HRR+ and BRCA1/2+ identified by either plasma or tissue based assays are sufficient to guide treatment decisions
Presented by: Gerhardt Attard, MD, PhD, University College London Cancer Institute, London, United Kingdom
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2023 European Society of Medical Oncology (ESMO) Annual Meeting, Madrid, Spain, Fri, Oct 20 – Tues, Oct 24, 2023.
References:
- Chi KN, Rathkopf D, Smith MR, et al. Niraparib and abiraterone acetate for metastatic castration-resistant prostate cancer. J Clin Oncol. 2023 Jun 20;41(18):3339-3351.
- Efstathiou E, Smith MR, Sandhu S, et al. Niraparib (NIRA) with abiraterone acetate and prednisone (AAP) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alterations: Second interim analysis (IA2) of MAGNITUDE. J Clin Oncol. 2023;41(suppl 6):170.