Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer.

Metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease with current standard-of-care therapies. Homologous recombination repair (HRR) gene alterations, including BRCA1/2 alterations, can sensitize cancer cells to poly (ADP-ribose) polymerase inhibition, which may improve outcomes in treatment-naïve mCRPC when combined with androgen receptor signaling inhibition.

MAGNITUDE (ClinicalTrials.gov identifier: NCT03748641) is a phase III, randomized, double-blinded study that evaluates niraparib and abiraterone acetate plus prednisone (niraparib + AAP) in patients with (HRR+, n = 423) or without (HRR-, n = 247) HRR-associated gene alterations, as prospectively determined by tissue/plasma-based assays. Patients were assigned 1:1 to receive niraparib + AAP or placebo + AAP. The primary end point, radiographic progression-free survival (rPFS) assessed by central review, was evaluated first in the BRCA1/2 subgroup and then in the full HRR+ cohort, with secondary end points analyzed for the full HRR+ cohort if rPFS was statistically significant. A futility analysis was preplanned in the HRR- cohort.

Median rPFS in the BRCA1/2 subgroup was significantly longer in the niraparib + AAP group compared with the placebo + AAP group (16.6 v 10.9 months; hazard ratio [HR], 0.53; 95% CI, 0.36 to 0.79; P = .001). In the overall HRR+ cohort, rPFS was significantly longer in the niraparib + AAP group compared with the placebo + AAP group (16.5 v 13.7 months; HR, 0.73; 95% CI, 0.56 to 0.96; P = .022). These findings were supported by improvement in the secondary end points of time to symptomatic progression and time to initiation of cytotoxic chemotherapy. In the HRR- cohort, futility was declared per the prespecified criteria. Treatment with niraparib + AAP was tolerable, with anemia and hypertension as the most reported grade ≥ 3 adverse events.

Combination treatment with niraparib + AAP significantly lengthened rPFS in patients with HRR+ mCRPC compared with standard-of-care AAP.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2023 Mar 23 [Epub ahead of print]

Kim N Chi, Dana Rathkopf, Matthew R Smith, Eleni Efstathiou, Gerhardt Attard, David Olmos, Ji Youl Lee, Eric J Small, Andrea J Pereira de Santana Gomes, Guilhem Roubaud, Marniza Saad, Bogdan Zurawski, Valerii Sakalo, Gary E Mason, Peter Francis, George Wang, Daphne Wu, Brooke Diorio, Angela Lopez-Gitlitz, Shahneen Sandhu, MAGNITUDE Principal Investigators

BC Cancer - Vancouver Center, University of British Columbia, Vancouver, BC, Canada., Memorial Sloan Kettering Cancer Center and Weill Cornell Medicine, New York, NY., Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA., Houston Methodist Cancer Center, Houston, TX., University College London, London, UK., Department of Medical Oncology, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain., Department of Urology Cancer Center, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, South Korea., Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA., Liga Norte Riograndense Contra o Câncer, Natal, Brazil., Department of Medical Oncology, Institut Bergonié, Bordeaux, France., Department of Clinical Oncology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia., Department of Outpatient Chemotherapy, Professor Franciszek Lukaszczyk Oncology Center, Bydgoszcz, Poland., Kyiv City Clinical Oncology Center and Academician O.F. Vozianov Institute of Urology of the National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine., Janssen Research & Development, LLC, Spring House, PA., Janssen Research & Development, LLC, Raritan, NJ., Janssen Research & Development, LLC, Los Angeles, CA., Janssen Research & Development, LLC, Titusville, NJ., Peter MacCallum Cancer Centre and the University of Melbourne, Melbourne, Australia.