Clinical cancer research : an official journal of the American Association for Cancer Research · 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.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАКомментарийНазвание и аннотация: Перевод в очереди
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Turner Nicholas C, Balmaña Judith, Poncet Coralie, Goulioti Theodora, Tryfonidis Konstantinos, Honkoop Aafke H, Zoppoli Gabriele, Razis Evangelia, Johannsson Oskar T, Colleoni Marco, Tutt Andrew N, Audeh William, Ignatiadis Michail, Mailliez Audrey, Trédan Olivier, Musolino Antonino, Vuylsteke Peter, Juan-Fita Maria Jose, Macpherson Iain R J, Kaufman Bella, Manso Luis, Goldstein Lori J, Ellard Susan L, Láng István, Jen Kai Yu, Adam Virginie, Litière Saskia, Erban John, Cameron David A, BRAVO Steering Committee and the BRAVO investigators
Аннотация
PURPOSE: 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.
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.