دورية أكاديمية
Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer
| العنوان: | Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer |
|---|---|
| المؤلفون: | Chi, Kim N, Rathkopf, Dana, Smith, Matthew R, Efstathiou, Eleni, Attard, Gerhardt, Olmos, David, Lee, Ji Youl, Small, Eric J, Pereira de Santana Gomes, Andrea J, Roubaud, Guilhem, Saad, Marniza, Zurawski, Bogdan, Sakalo, Valerii, Mason, Gary E, Francis, Peter, Wang, George, Wu, Daphne, Diorio, Brooke, Lopez-Gitlitz, Angela, Sandhu, Shahneen, MAGNITUDE Principal Investigators |
| المصدر: | Journal of Clinical Oncology (2023) (In press). |
| بيانات النشر: | American Society of Clinical Oncology (ASCO) |
| سنة النشر: | 2023 |
| المجموعة: | University College London: UCL Discovery |
| مصطلحات موضوعية: | MAGNITUDE Principal Investigators |
| الوصف: | 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-naïve 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 ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text |
| اللغة: | English |
| العلاقة: | https://discovery.ucl.ac.uk/id/eprint/10167403/1/jco.22.01649.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10167403Test/ |
| الإتاحة: | https://discovery.ucl.ac.uk/id/eprint/10167403/1/jco.22.01649.pdfTest https://discovery.ucl.ac.uk/id/eprint/10167403Test/ |
| حقوق: | open |
| رقم الانضمام: | edsbas.19165071 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |