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 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

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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

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Breast Neoplasms
Neoplasm Metastasis
Brain Neoplasms
Survival
Brain
eribulin
docetaxel
gemcitabine
Topoisomerase I Inhibitors
etirinotecan pegol
Anthracyclines
Risk Reduction Behavior
Paclitaxel
Polymers
Survival Rate
Technology
Physicians
Drug Therapy
Therapeutics
Population

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

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. / Cortés, Javier; Rugo, Hope S.; Awada, Ahmad; Twelves, Chris; Perez, Edith A.; Im, Seock–ah; Gómez-Pardo, Patricia; Schwartzberg, Lee; Diéras, 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.

In: Breast Cancer Research and Treatment, Vol. 165, No. 2, 01.09.2017, p. 329-341.

Research output: Contribution to journalArticle

Cortés, J, Rugo, HS, Awada, A, Twelves, C, Perez, EA, Im, S, Gómez-Pardo, P, Schwartzberg, L, Diéras, V, Yardley, DA, Potter, DA, Mailliez, A, Moreno-Aspitia, A, Ahn, JS, Zhao, C, Hoch, U, Tagliaferri, M, Hannah, AL & 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, vol. 165, no. 2, pp. 329-341. https://doi.org/10.1007/s10549-017-4304-7
Cortés, Javier ; Rugo, Hope S. ; Awada, Ahmad ; Twelves, Chris ; Perez, Edith A. ; Im, Seock–ah ; Gómez-Pardo, Patricia ; Schwartzberg, Lee ; Diéras, 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. / 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. In: Breast Cancer Research and Treatment. 2017 ; Vol. 165, No. 2. pp. 329-341.
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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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T1 - Prolonged survival in patients with breast cancer and a history of brain metastases

T2 - results of a preplanned subgroup analysis from the randomized phase III BEACON trial

AU - Cortés, Javier

AU - Rugo, Hope S.

AU - Awada, Ahmad

AU - Twelves, Chris

AU - Perez, Edith A.

AU - Im, Seock–ah

AU - Gómez-Pardo, Patricia

AU - Schwartzberg, Lee

AU - Diéras, Veronique

AU - Yardley, Denise A.

AU - Potter, David A.

AU - Mailliez, Audrey

AU - Moreno-Aspitia, Alvaro

AU - Ahn, Jin Seok

AU - Zhao, Carol

AU - Hoch, Ute

AU - Tagliaferri, Mary

AU - Hannah, Alison L.

AU - O’Shaughnessy, Joyce

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Y1 - 2017/9/1

N2 - 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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