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 journalArticlepeer-review

26 Scopus citations


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 ( NCT02915744).

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

Bibliographical note

Funding Information:
We thank the patients, their caregivers and families, and the investigators who participated in this study. We thank the independent Data Monitoring Committee (Drs Kathy Miller, Banu Arun, and James Boyett) for their study oversight. We also thank Phillips Gilmore Oncology Communications for providing medical writing support, funded by Nektar Therapeutics. This study was sponsored by Nektar Therapeutics, San Francisco, CA, USA.

Publisher Copyright:
© 2017, The Author(s).


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

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