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Sandy Srinivas, MD


More MAGNITUDE Results in Prostate Cancer With Niraparib for Additional HRR Alterations

By: Celeste L. Dixon
Posted: Monday, March 20, 2023

Expanding on previous results of the phase III MAGNITUDE study focusing on BRCA1/2 alterations, investigators performing a gene-by-gene analysis found that the PARP inhibitor niraparib plus abiraterone acetate and prednisone was active in patients with metastatic castration-resistant prostate cancer and a single-gene homologous recombination repair (HRR) alteration other than BRCA1/2. Overall, radiographic progression-free survival, the primary endpoint, was statistically significantly and clinically meaningfully improved with this strategy, reported Kim N. Chi, MD, of the University of British Columbia, Vancouver, and colleagues during the Journal of the Advanced Practitioner in Oncology conference JADPRO Live (Abstract JL1015E).

“Improvements in the secondary endpoints, such as delaying time to cytotoxic chemotherapy and prolonging time to symptomatic progression, are particularly relevant for improving the experience of patients with [metastatic castration-resistant prostate cancer],” the authors stated.

The analyzed cohort included 186 patients with metastatic castration-resistant prostate cancer and an alteration in the ATM, BRIP1, CDK12, CHEK2, FANCA, HDAC2, or PALB2 gene (excluding co-occurring alterations). A total of 91 patients were randomly assigned to receive niraparib plus abiraterone acetate and prednisone, and 95 patients received placebo plus abiraterone acetate and prednisone.

Patients with PALB2, CHEK2, and HDAC2 alterations, like those with BRCA1/2 gene alterations, had consistent improvement across all endpoints: the primary endpoint of radiographic progression–free survival; the secondary endpoints (time to cytotoxic chemotherapy, time to symptomatic disease progression, and overall survival); and time to prostate-specific antigen (PSA) progression and overall response rate. Patients with ATM alterations experienced benefits in all of those endpoints except radiographic progression–free and overall survival. Patients with CDK12 alterations experienced benefits only in the time to PSA progression and overall response rate.

“When combined into functional groups, patients with an alteration in the HRR-Fanconi pathway (BRIP1, FANCA, and PALB2) [and] patients with an HRR-associated alteration (CHEK2 or HDAC2)” were similar, pointed out Dr. Chi and co-investigators. These patients “showed improvement in all endpoints.”

Disclosure: The study authors’ disclosure information can be found at

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