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

作者：Cortes Javier; Rugo Hope S; Awada Ahmad; Twelves Chris; Perez Edith A; Im Seock Ah; Gomez Pardo Patricia; Schwartzberg Lee S; Dieras Veronique; Yardley Denise A; Potter David A; Mailliez Audrey; Moreno Aspitia Alvaro; Ahn Jin Seok; Zhao Carol; Hoch Ute; Tagliaferri Mary; Hannah Alison L; O'Shaughnessy Joyce^*

来源：Breast Cancer Research and Treatment, 2017, 165(2): 329-341.

DOI：10.1007/s10549-017-4304-7

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

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

• 出版日期2017-9