Niraparib for advanced breast cancer with germline BRCA1 and BRCA2 mutations: the EORTC 1307-BCG/BIG5-13/TESARO PR-30-50-10-C BRAVO study

Turner, N. C. et al. (2021) Niraparib for advanced breast cancer with germline BRCA1 and BRCA2 mutations: the EORTC 1307-BCG/BIG5-13/TESARO PR-30-50-10-C BRAVO study. Clinical Cancer Research, 27(20), pp. 5482-5491. (doi: 10.1158/1078-0432.CCR-21-0310) (PMID:34301749) (PMCID:PMC8530899)

Abstract

Purpose: To investigate the activity of niraparib in patients with germline-mutated BRCA1/2 (gBRCAm) advanced breast cancer (aBC). Patients and methods: BRAVO was a randomized, open-label phase 3 trial. Eligible patients had gBRCAm and HER2-negative aBC previously treated with {less than or equal to}2 prior lines of chemotherapy for aBC or had relapsed within 12 months of adjuvant chemotherapy, and were randomised 2:1 between niraparib and physician's choice chemotherapy (PC) (monotherapy with eribulin, capecitabine, vinorelbine, or gemcitabine). Patients with hormone-receptor positive tumours had to have received {greater than or equal to}1 line of endocrine therapy and progressed during this treatment in the metastatic setting or relapsed within one year of neo/adjuvant treatment. The primary endpoint was centrally-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), PFS by local assessment, objective response rate (ORR), and safety. Results: After the pre-planned interim analysis, recruitment was halted based on futility, noting a high degree of discordance between local and central PFS assessment in the PC arm that resulted in informative censoring. At the final analysis (median follow-up: 19.9 months), median centrally-assessed PFS was 4.1 months in the niraparib arm (n=141) versus 3.1 months in the PC arm (n=74; hazard ratio [HR] 0.96; 95% CI: 0.65-1.44; P=0.86). HRs for OS and local-PFS were 0.95 (95% CI 0.63-1.42) and 0.65 (0.46-0.93), respectively. ORR was 35% (95% CI 26-45) with niraparib and 31% (19-46) in the PC arm. Conclusion: Informative censoring in the control arm prevented accurate assessment of the trial hypothesis, although there was clear evidence of niraparib's activity in this patient population.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: MacPherson, Professor Iain
• Authors: Turner, N. C., Balmaña, J., Poncet, C., Goulioti, T., Tryfonidis, K., Honkoop, A. H., Zoppoli, G., Razis, E., Johannsson, O. T., Colleoni, M., Tutt, A. N. J., AUDEH, W., Ignatiadis, M., Mailliez, A., Trédan, O., Musolino, A., Vuylsteke, P., Juan Fita, M. J., Macpherson, I. R.J., Kaufman, B., Manso, L., Goldstein, L. J., Ellard, S. L., Láng, I., Jen, K. Y., Adam, V., Litière, S., Erban, J., and Cameron, D. A.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Clinical Cancer Research
• Publisher: American Association for Cancer Research
• ISSN: 1078-0432
• ISSN (Online): 1557-3265
• Published Online: 22 July 2021
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in Clinical Cancer Research 27(20): 5482-5491
• Publisher Policy: Reproduced under a Creative Commons License