Niraparib Combination Shows Promise in Aggressive Prostate Cancer, Phase 3 Trial Reveals
BOSTON – A new combination therapy of Niraparib and abiraterone acetate plus prednisone demonstrated a statistically notable and clinically meaningful improvement in radiographic progression-free survival (rPFS) in patients with HRR-deficient metastatic castration-sensitive prostate cancer (mCSPC), according to results from a randomized Phase 3 trial presented today. The findings offer a potential new treatment avenue for a particularly aggressive form of prostate cancer, where limited options currently exist.
Prostate cancer is the moast common cancer in men, with mCSPC representing an advanced stage where the disease has spread and no longer responds to hormone therapy alone. Approximately 20-30% of mCSPC cases harbor alterations in homologous recombination repair (HRR) genes, making them susceptible to PARP inhibitors like Niraparib. This trial, known as MAGNITUDE, investigated whether adding Niraparib to standard treatment-abiraterone acetate and prednisone-could extend the time before the cancer progresses.
The MAGNITUDE trial randomized 404 patients with HRR-deficient mCSPC to receive either Niraparib plus abiraterone acetate and prednisone, or abiraterone acetate and prednisone alone. Results showed a hazard ratio of 0.64 (95% confidence interval, 0.49-0.84; P=0.0014) favoring the Niraparib combination, representing a 36% reduction in the risk of disease progression or death. Median rPFS was 16.5 months with Niraparib versus 8.3 months with abiraterone acetate and prednisone.
While overall survival data are not yet mature, preliminary analyses suggest a trend towards improved survival with the Niraparib combination. The most common adverse events associated with Niraparib were anemia, fatigue, and nausea, consistent with the known safety profile of PARP inhibitors.
The study investigators included M.Ö., A.G., K.V., H.L., G.T.G., H.H.C., W.K., C.R.V., D.S., K.K., S.L., B.B., F.S., S.D.M., S.A.M., D.O., K.N.C., and D.E.R. Disclosures reveal extensive financial ties between many investigators and pharmaceutical companies including AstraZeneca, Johnson & Johnson, Merck, Pfizer, Janssen, Bayer, Roche, and others. M.Ö. reports consulting/advisory roles with Astellas Pharma, AstraZeneca and MSD Oncology; honoraria from Astellas Pharma, janssen Oncology and Novartis; and speaker’s bureau role and travel expenses from AstraZeneca. A.G. reports consulting/advisory roles with bayer and Janssen Oncology; speaker’s bureau roles with Astellas Pharma, AstraZeneca, Bayer and Janssen Oncology; honoraria from Adium Pharma, Astellas Pharma, AstraZeneca, Bayer and Janssen Oncology; research funding from AstraZeneca, Bayer, janssen Oncology, MSD Oncology and Roche; and travel expenses from Janssen Oncology. K.V. reports consulting/advisory roles with Adium Pharma, AstraZeneca and Roche/Genentech; speaker’s bureau roles with AstraZeneca, Bayer, Bristol Myers Squibb Brazil, GlaxoSmithKline, Knight Pharmaceuticals, Pfizer, Roche/Genentech and Servier; institutional research funding from AstraZeneca, BeiGene, bristol Myers Squibb Brazil, Gilead Sciences, Incyte, Janssen Oncology, Lilly, MSD Oncology, Roche/Genentech, Seagen and Servier; and travel expenses from AstraZeneca, MSD Oncology and roche/Genentech. H.L. has no conflicts of interest to report. G.T.G. reports consulting/advisory roles with Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb, EMD Serono, Ferring, Janssen, Merck, Novartis, Pfizer and Tolmar; honoraria from Astellas Pharma, AstraZeneca, Bayer, Janssen, Merck and Tolmar; and travel expenses from Janssen and Pfizer. H.H.C.reports a consulting/advisory role with janssen Oncology; institutional research funding from Clovis Oncology, Janssen, Promontory Therapeutics and Sanofi; and royalties from UpToDate. W.K., C.R.V., D.S., K.K., S.L., B.B., F.S., S.D.M. and S.A.M. are employees of Johnson & Johnson with stock ownership. D.O. reports consulting/advisory roles with AstraZeneca, Bayer, Janssen, MSD Oncology and Pfizer; honoraria from Bayer and
