Data from Niraparib for Advanced Breast Cancer with Germline &lt;i&gt;BRCA1&lt;/i&gt; and &lt;i&gt;BRCA2&lt;/i&gt; Mutations: the EORTC 1307-BCG/BIG5–13/TESARO PR-30–50–10-C BRAVO Study

Aafke H Honkoop,Lori J Goldstein,Theodora Goulioti,Marco Colleoni,Gabriele Zoppoli,Nicholas C Turner,Olivier Trédan,Virginie Adam,Konstantinos Tryfonidis,Coralie Poncet,Michail Ignatiadis,Saskia Litière,Evangelia Razis,William Audeh,Audrey Mailliez,Peter Vuylsteke,Bella Kaufman,Antonino Musolino,Kuang Yu Jen ,John K Erban ,Óskar T Jóhannsson ,Andrew Tutt ,István Làng ,Iain R Macpherson ,Susan Ellard ,Judith Balmañà ,María José Juan-Fita ,Luís Manso ,David Cameron

doi:10.1158/1078-0432.c.6778139

Abstract

<div>AbstractPurpose:To investigate the activity of niraparib in patients with germline-mutated BRCA1/2 (gBRCAm) advanced breast cancer.Patients and Methods:BRAVO was a randomized, open-label phase III trial. Eligible patients had gBRCAm and HER2-negative advanced breast cancer previously treated with ≤2 prior lines of chemotherapy for advanced breast cancer or had relapsed within 12 months of adjuvant chemotherapy, and were randomized 2:1 between niraparib and physician's choice chemotherapy (PC; monotherapy with eribulin, capecitabine, vinorelbine, or gemcitabine). Patients with hormone receptor–positive tumors had to have received ≥1 line of endocrine therapy and progressed during this treatment in the metastatic setting or relapsed within 1 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 (local-PFS), objective response rate (ORR), and safety.Results:After the pre-planned interim analysis, recruitment was halted on the basis of 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% confidence interval (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 (95% CI, 0.46–0.93), respectively. ORR was 35% (95% CI, 26–45) with niraparib and 31% (95% CI, 19–46) in the PC arm.Conclusions: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.</div>

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