Ixabepilone alone or with cetuximab as first-line treatment for advanced/metastatic triple-negative breast cancer

Olivier Trédan, Mario Campone, Jacek Jassem, Rostislav Vyzula, Bruno Coudert, Carmen Pacilio, Jana Prausova, Anne Claire Hardy-Bessard, Ana Arance, Pralay Mukhopadhyay, Alessandra Aloe, Henri Roché

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Background Despite high initial sensitivity to chemotherapy, TNBC is associated with a poor prognosis, highlighting the need for novel therapeutic strategies. The aim of this multicenter, randomized, open-label phase II trial was to assess the efficacy of ixabepilone as monotherapy, and the combination of ixabepilone with cetuximab, as first-line treatment in patients with triple-negative locally advanced nonresectable and/or metastatic breast cancer.

Patients and Methods Women were randomly assigned to receive either ixabepilone (40 mg/m2) every 21 days (n = 40), or ixabepilone (40 mg/m2) every 21 days with cetuximab (400 mg/m2 loading dose, followed by 250 mg/m2) once weekly (n = 39). The primary end point of the trial was to estimate the response rates of ixabepilone monotherapy and ixabepilone with cetuximab combination therapy.

Results Of 79 randomized patients, 77 were treated. Based on an intent-to-treat analysis, an objective response rate of 30% (95% confidence interval [CI], 16.6-46.5) was observed in the monotherapy arm, and 35.9% (95% CI, 21.2-52.8) in the combination arm. Median progression-free survival was 4.1 months in both treatment groups. Safety findings were consistent with the known individual toxicity profiles of ixabepilone and cetuximab. Skin and subcutaneous tissue disorders were more common with combination therapy, as were discontinuations because of adverse events.

Conclusion Ixabepilone monotherapy and the ixabepilone and cetuximab combination demonstrated similar levels of clinical activity in first-line treatment of advanced TNBC, with a predictable safety profile. Further investigation of novel therapies for TNBC is required to improve patient outcomes.

Original languageEnglish
Pages (from-to)8-15
Number of pages8
JournalClinical Breast Cancer
Volume15
Issue number1
DOIs
Publication statusPublished - Feb 1 2015

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Triple Negative Breast Neoplasms
Therapeutics
Confidence Intervals
Safety
ixabepilone
Cetuximab
Subcutaneous Tissue
Disease-Free Survival
Breast Neoplasms
Drug Therapy

Keywords

  • Cetuximab
  • EGFR
  • Ixabepilone
  • Metastatic breast cancer
  • Triple negative

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Ixabepilone alone or with cetuximab as first-line treatment for advanced/metastatic triple-negative breast cancer. / Trédan, Olivier; Campone, Mario; Jassem, Jacek; Vyzula, Rostislav; Coudert, Bruno; Pacilio, Carmen; Prausova, Jana; Hardy-Bessard, Anne Claire; Arance, Ana; Mukhopadhyay, Pralay; Aloe, Alessandra; Roché, Henri.

In: Clinical Breast Cancer, Vol. 15, No. 1, 01.02.2015, p. 8-15.

Research output: Contribution to journalArticle

Trédan, O, Campone, M, Jassem, J, Vyzula, R, Coudert, B, Pacilio, C, Prausova, J, Hardy-Bessard, AC, Arance, A, Mukhopadhyay, P, Aloe, A & Roché, H 2015, 'Ixabepilone alone or with cetuximab as first-line treatment for advanced/metastatic triple-negative breast cancer', Clinical Breast Cancer, vol. 15, no. 1, pp. 8-15. https://doi.org/10.1016/j.clbc.2014.07.007
Trédan, Olivier ; Campone, Mario ; Jassem, Jacek ; Vyzula, Rostislav ; Coudert, Bruno ; Pacilio, Carmen ; Prausova, Jana ; Hardy-Bessard, Anne Claire ; Arance, Ana ; Mukhopadhyay, Pralay ; Aloe, Alessandra ; Roché, Henri. / Ixabepilone alone or with cetuximab as first-line treatment for advanced/metastatic triple-negative breast cancer. In: Clinical Breast Cancer. 2015 ; Vol. 15, No. 1. pp. 8-15.
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abstract = "Background Despite high initial sensitivity to chemotherapy, TNBC is associated with a poor prognosis, highlighting the need for novel therapeutic strategies. The aim of this multicenter, randomized, open-label phase II trial was to assess the efficacy of ixabepilone as monotherapy, and the combination of ixabepilone with cetuximab, as first-line treatment in patients with triple-negative locally advanced nonresectable and/or metastatic breast cancer.Patients and Methods Women were randomly assigned to receive either ixabepilone (40 mg/m2) every 21 days (n = 40), or ixabepilone (40 mg/m2) every 21 days with cetuximab (400 mg/m2 loading dose, followed by 250 mg/m2) once weekly (n = 39). The primary end point of the trial was to estimate the response rates of ixabepilone monotherapy and ixabepilone with cetuximab combination therapy.Results Of 79 randomized patients, 77 were treated. Based on an intent-to-treat analysis, an objective response rate of 30{\%} (95{\%} confidence interval [CI], 16.6-46.5) was observed in the monotherapy arm, and 35.9{\%} (95{\%} CI, 21.2-52.8) in the combination arm. Median progression-free survival was 4.1 months in both treatment groups. Safety findings were consistent with the known individual toxicity profiles of ixabepilone and cetuximab. Skin and subcutaneous tissue disorders were more common with combination therapy, as were discontinuations because of adverse events.Conclusion Ixabepilone monotherapy and the ixabepilone and cetuximab combination demonstrated similar levels of clinical activity in first-line treatment of advanced TNBC, with a predictable safety profile. Further investigation of novel therapies for TNBC is required to improve patient outcomes.",
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AU - Trédan, Olivier

AU - Campone, Mario

AU - Jassem, Jacek

AU - Vyzula, Rostislav

AU - Coudert, Bruno

AU - Pacilio, Carmen

AU - Prausova, Jana

AU - Hardy-Bessard, Anne Claire

AU - Arance, Ana

AU - Mukhopadhyay, Pralay

AU - Aloe, Alessandra

AU - Roché, Henri

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N2 - Background Despite high initial sensitivity to chemotherapy, TNBC is associated with a poor prognosis, highlighting the need for novel therapeutic strategies. The aim of this multicenter, randomized, open-label phase II trial was to assess the efficacy of ixabepilone as monotherapy, and the combination of ixabepilone with cetuximab, as first-line treatment in patients with triple-negative locally advanced nonresectable and/or metastatic breast cancer.Patients and Methods Women were randomly assigned to receive either ixabepilone (40 mg/m2) every 21 days (n = 40), or ixabepilone (40 mg/m2) every 21 days with cetuximab (400 mg/m2 loading dose, followed by 250 mg/m2) once weekly (n = 39). The primary end point of the trial was to estimate the response rates of ixabepilone monotherapy and ixabepilone with cetuximab combination therapy.Results Of 79 randomized patients, 77 were treated. Based on an intent-to-treat analysis, an objective response rate of 30% (95% confidence interval [CI], 16.6-46.5) was observed in the monotherapy arm, and 35.9% (95% CI, 21.2-52.8) in the combination arm. Median progression-free survival was 4.1 months in both treatment groups. Safety findings were consistent with the known individual toxicity profiles of ixabepilone and cetuximab. Skin and subcutaneous tissue disorders were more common with combination therapy, as were discontinuations because of adverse events.Conclusion Ixabepilone monotherapy and the ixabepilone and cetuximab combination demonstrated similar levels of clinical activity in first-line treatment of advanced TNBC, with a predictable safety profile. Further investigation of novel therapies for TNBC is required to improve patient outcomes.

AB - Background Despite high initial sensitivity to chemotherapy, TNBC is associated with a poor prognosis, highlighting the need for novel therapeutic strategies. The aim of this multicenter, randomized, open-label phase II trial was to assess the efficacy of ixabepilone as monotherapy, and the combination of ixabepilone with cetuximab, as first-line treatment in patients with triple-negative locally advanced nonresectable and/or metastatic breast cancer.Patients and Methods Women were randomly assigned to receive either ixabepilone (40 mg/m2) every 21 days (n = 40), or ixabepilone (40 mg/m2) every 21 days with cetuximab (400 mg/m2 loading dose, followed by 250 mg/m2) once weekly (n = 39). The primary end point of the trial was to estimate the response rates of ixabepilone monotherapy and ixabepilone with cetuximab combination therapy.Results Of 79 randomized patients, 77 were treated. Based on an intent-to-treat analysis, an objective response rate of 30% (95% confidence interval [CI], 16.6-46.5) was observed in the monotherapy arm, and 35.9% (95% CI, 21.2-52.8) in the combination arm. Median progression-free survival was 4.1 months in both treatment groups. Safety findings were consistent with the known individual toxicity profiles of ixabepilone and cetuximab. Skin and subcutaneous tissue disorders were more common with combination therapy, as were discontinuations because of adverse events.Conclusion Ixabepilone monotherapy and the ixabepilone and cetuximab combination demonstrated similar levels of clinical activity in first-line treatment of advanced TNBC, with a predictable safety profile. Further investigation of novel therapies for TNBC is required to improve patient outcomes.

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KW - EGFR

KW - Ixabepilone

KW - Metastatic breast cancer

KW - Triple negative

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