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. 2017 Sep;165(2):329-341.
doi: 10.1007/s10549-017-4304-7. Epub 2017 Jun 13.

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  1 , Hope S Rugo  2 , Ahmad Awada  3 , Chris Twelves  4 , Edith A Perez  5 , Seock-Ah Im  6 , Patricia Gómez-Pardo  7 , Lee S Schwartzberg  8 , Veronique Diéras  9 , Denise A Yardley  10 , David A Potter  11 , Audrey Mailliez  12 , Alvaro Moreno-Aspitia  1 , Jin-Seok Ahn  13 , Carol Zhao  14 , Ute Hoch  14 , Mary Tagliaferri  14 , Alison L Hannah  15 , Joyce O'Shaughnessy  16
Affiliations

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 et al. Breast Cancer Res Treat. 2017 Sep.

Erratum in

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).

Trial registration: ClinicalTrials.gov NCT01492101.

Keywords: Brain metastases; Chemotherapy; Etirinotecan pegol; Metastatic breast cancer; NKTR-102.

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Conflict of interest statement

JC: advisor: Celgene, Roche; speaker: Celgene, Roche, Eisai, Novartis; partner and stockholder: MedSIR. HSR: research support to UC Regents from Eisai and from Nektar for this trial. AA: advisor: Nektar Therapeutics, Roche, Bayer, Pfizer. CJT: advisor: Nektar Therapeutics. VD: advisor: Roche, Novartis, Pfizer, Nektar, Eisai, Lilly; speaker: Roche, Pfizer, Novartis. CZ, MT, and UH: paid employees of Nektar Therapeutics. ALH: consultant, Nektar Therapeutics. JO: advisor: Nektar Therapeutics. EAP, S-AI, LSS, PG-P, DAY, DAP, AM, AM-A, and J-SA declare no conflicts of interest.

Figures

Fig. 1
Fig. 1
Kaplan–Meier estimates for a overall survival and b progression-free survival for patients with stable, treated brain metastases; and c overall survival for patients with radiologically detectable, but stable, brain lesions at study entry. CI confidence interval, HR hazard ratio, mOS median overall survival, mPFS median progression-free survival, TPC treatment of physician’s choice
Fig. 2
Fig. 2
Forest plot of hazard ratios (HR) with 95% confidence intervals (CI) for overall survival for selected prognostic factors in the intention-to-treat (ITT) population with a history of treated, stable brain metastases. BC breast cancer, CI confidence interval, ECOG Eastern Cooperative Oncology Group, HER2 human epidermal growth factor receptor 2, HR hazard ratio, TPC treatment of physician’s choice
See this image and copyright information in PMC

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