Niraparib plus abiraterone acetate with prednisone in patients with metastatic castration-resistant prostate cancer and homologous recombination repair gene alterations: second interim analysis of the randomized phase III MAGNITUDE trial

Chi, KN; Sandhu, S; Smith, MR; Attard, G; Saad, M; Olmos, D; Castro, E; Roubaud, G; Pereira de Santana Gomes, AJ; Small, EJ; Rathkopf, DE; Gurney, H; Jung, W; Mason, GE; Dibaj, S; Wu, D; Diorio, B; Urtishak, K; Del Corral, A; Francis, P; Kim, W; Efstathiou, E

Author(s): Chi, KN; Sandhu, S; Smith, MR; Attard, G; Saad, M; Olmos, D; Castro, E; Roubaud, G; Pereira de Santana Gomes, AJ; Small, EJ; Rathkopf, DE; Gurney, H; Jung, W; Mason, GE; Dibaj, S; Wu, D; Diorio, B; Urtishak, K; Del Corral, A; Francis, P; Kim, W; Efstathiou, E;
Details: Publication Year 2023-09,Volume 34,Issue #9,Page 772-782
Journal Title: Annals of Oncology
Publication Type: Research article
Abstract: BACKGROUND: Patients with metastatic castration-resistant prostate cancer (mCRPC) and BRCA alterations have poor outcomes. MAGNITUDE found patients with homologous recombination repair gene alterations (HRR+), particularly BRCA1/2, benefit from first-line therapy with niraparib plus abiraterone acetate and prednisone (AAP). Here we report longer follow-up from the second prespecified interim analysis (IA2). PATIENTS AND METHODS: Patients with mCRPC were prospectively identified as HRR+ with/without BRCA1/2 alterations and randomized 1 : 1 to niraparib (200 mg orally) plus AAP (1000 mg/10 mg orally) or placebo plus AAP. At IA2, secondary endpoints [time to symptomatic progression, time to initiation of cytotoxic chemotherapy, overall survival (OS)] were assessed. RESULTS: Overall, 212 HRR+ patients received niraparib plus AAP (BRCA1/2 subgroup, n = 113). At IA2 with 24.8 months of median follow-up in the BRCA1/2 subgroup, niraparib plus AAP significantly prolonged radiographic progression-free survival rPFS; blinded independent central review; median rPFS 19.5 versus 10.9 months; hazard ratio (HR) = 0.55 [95% confidence interval (CI) 0.39-0.78]; nominal P = 0.0007 consistent with the first prespecified interim analysis. rPFS was also prolonged in the total HRR+ population [HR = 0.76 (95% CI 0.60-0.97); nominal P = 0.0280; median follow-up 26.8 months]. Improvements in time to symptomatic progression and time to initiation of cytotoxic chemotherapy were observed with niraparib plus AAP. In the BRCA1/2 subgroup, the analysis of OS with niraparib plus AAP demonstrated an HR of 0.88 (95% CI 0.58-1.34; nominal P = 0.5505); the prespecified inverse probability censoring weighting analysis of OS, accounting for imbalances in subsequent use of poly adenosine diphosphate-ribose polymerase inhibitors and other life-prolonging therapies, demonstrated an HR of 0.54 (95% CI 0.33-0.90; nominal P = 0.0181). No new safety signals were observed. CONCLUSIONS: MAGNITUDE, enrolling the largest BRCA1/2 cohort in first-line mCRPC to date, demonstrated improved rPFS and other clinically relevant outcomes with niraparib plus AAP in patients with BRCA1/2-altered mCRPC, emphasizing the importance of identifying this molecular subset of patients.
Publisher: Elsevier
Keywords: Male; Humans; *Abiraterone Acetate; Prednisone; *Prostatic Neoplasms, Castration-Resistant/drug therapy/genetics; BRCA1 Protein/genetics; Recombinational DNA Repair; Treatment Outcome; BRCA2 Protein/genetics; Antineoplastic Combined Chemotherapy Protocols/therapeutic use; Brca; abiraterone acetate; homologous recombination repair; metastatic castration-resistant prostate cancer; niraparib
Department(s): Medical Oncology
PubMed ID: 37399894
Publisher's Version: https://doi.org/10.1016/j.annonc.2023.06.009
Open Access at Publisher's Site: https://doi.org/10.1016/j.annonc.2023.06.009
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-10-17 06:55:49

Last Modified: 2023-10-17 06:58:32