Chi, Kim N. and Rathkopf, Dana and Smith, Matthew R. and Efstathiou, Eleni and Attard, Gerhardt and Olmos, David and Lee, Ji Youl and Small, Eric J. and Gomes, Andrea J. Pereira De Santana and Roubaud, Guilhem and Saad, Marniza and Zurawski, Bogdan and Sakalo, Valerii and Mason, Gary E. and Francis, Peter and Ms, George Wang and Wu, Daphne and Diorio, Brooke and Lopez-Gitlitz, Angela and Sandhu, Shahneen and Invest, Magnitude Principal (2023) Niraparib and abiraterone acetate for metastatic castration-resistant prostate cancer. Journal of Clinical Oncology, 41 (18). 3339+. ISSN 0732-183X, DOI https://doi.org/10.1200/JCO.22.01649.
Full text not available from this repository.Abstract
PURPOSE 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-naive mCRPC when combined with androgen receptor signaling inhibition.METHODS 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.RESULTS 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.CONCLUSION Combination treatment with niraparib + AAP significantly lengthened rPFS in patients with HRR+ mCRPC compared with standard-of-care AAP.
| Item Type: | Article |
|---|---|
| Funders: | Janssen Research amp; Development LLC |
| Additional Information: | ASCO Genitourinary Cancers Symposium, San Francisco, CA, FEB 17-19, 2022 |
| Uncontrolled Keywords: | Metastatic castration-resistant prostate cancer (mCRPC); Lethal disease; Cytotoxic chemotherapy |
| Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 08 Nov 2025 10:10 |
| Last Modified: | 08 Nov 2025 10:10 |
| URI: | http://eprints.um.edu.my/id/eprint/49756 |
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