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Open Access 01-09-2017 | Clinical trial

Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial

Authors: Javier Cortés, Hope S. Rugo, Ahmad Awada, Chris Twelves, Edith A. Perez, Seock–Ah Im, Patricia Gómez-Pardo, Lee S. Schwartzberg, Veronique Diéras, Denise A. Yardley, David A. Potter, Audrey Mailliez, Alvaro Moreno-Aspitia, Jin-Seok Ahn, Carol Zhao, Ute Hoch, Mary Tagliaferri, Alison L. Hannah, Joyce O’Shaughnessy

Published in: Breast Cancer Research and Treatment | Issue 2/2017

Abstract

Purpose

Conventional chemotherapy has limited activity in patients with breast cancer and brain metastases (BCBM). Etirinotecan pegol (EP), a novel long-acting topoisomerase-1 inhibitor, was designed using advanced polymer technology to preferentially accumulate in tumor tissue including brain metastases, providing sustained cytotoxic SN38 levels.

Methods

The phase 3 BEACON trial enrolled 852 women with heavily pretreated locally recurrent or metastatic breast cancer between 2011 and 2013. BEACON compared EP with treatment of physician’s choice (TPC; eribulin, vinorelbine, gemcitabine, nab-paclitaxel, paclitaxel, ixabepilone, or docetaxel) in patients previously treated with anthracycline, taxane, and capecitabine, including those with treated, stable brain metastases. The primary endpoint, overall survival (OS), was assessed in a pre-defined subgroup of BCBM patients; an exploratory post hoc analysis adjusting for the diagnosis-specific graded prognostic assessment (GPA) index was also conducted.

Results

In the trial, 67 BCBM patients were randomized (EP, n = 36; TPC, n = 31). Treatment subgroups were balanced for baseline characteristics and GPA indices. EP was associated with a significant reduction in the risk of death (HR 0.51; P < 0.01) versus TPC; median OS was 10.0 and 4.8 months, respectively. Improvement in OS was observed in both poorer and better GPA prognostic groups. Survival rates at 12 months were 44.4% for EP versus 19.4% for TPC. Consistent with the overall BEACON population, fewer patients on EP experienced grade ≥3 toxicity (50 vs. 70%).

Conclusions

The significant improvement in survival in BCBM patients provides encouraging data for EP in this difficult-to-treat subgroup of patients. A phase three trial of EP in BCBM patients is underway (ClinicalTrials.gov NCT02915744).

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Title: Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial
Authors: Javier Cortés
Hope S. Rugo
Ahmad Awada
Chris Twelves
Edith A. Perez
Seock–Ah Im
Patricia Gómez-Pardo
Lee S. Schwartzberg
Veronique Diéras
Denise A. Yardley
David A. Potter
Audrey Mailliez
Alvaro Moreno-Aspitia
Jin-Seok Ahn
Carol Zhao
Ute Hoch
Mary Tagliaferri
Alison L. Hannah
Joyce O’Shaughnessy
Publication date: 01-09-2017
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 2/2017
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-017-4304-7

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