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

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

Research output: Contribution to journalArticle

23 Scopus citations

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).

Original languageEnglish (US)
Pages (from-to)329-341
Number of pages13
JournalBreast Cancer Research and Treatment
Volume165
Issue number2
DOIs
StatePublished - Sep 1 2017

Keywords

  • Brain metastases
  • Chemotherapy
  • Etirinotecan pegol
  • Metastatic breast cancer
  • NKTR-102

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Cortés, J., Rugo, H. S., Awada, A., Twelves, C., Perez, E. A., Im, S., Gómez-Pardo, P., Schwartzberg, L. S., Diéras, V., Yardley, D. A., Potter, D. A., Mailliez, A., Moreno-Aspitia, A., Ahn, J. S., Zhao, C., Hoch, U., Tagliaferri, M., Hannah, A. L., & O’Shaughnessy, J. (2017). 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. Breast Cancer Research and Treatment, 165(2), 329-341. https://doi.org/10.1007/s10549-017-4304-7