Trastuzumab-associated cardiac events at 8 years of median follow-up in the herceptin adjuvant trial (BIG 1-01)

Evandro De Azambuja, Marion J. Procter, Dirk J. Van Veldhuisen, Dominique Agbor-Tarh, Otto Metzger-Filho, Jutta Steinseifer, Michael Untch, Ian E. Smith, Luca Gianni, Jose Baselga, Christian Jackisch, David A. Cameron, Richard Bell, Brian Leyland-Jones, Mitch Dowsett, Richard D. Gelber, Martine J. Piccart-Gebhart, Thomas M. Suter

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Abstract

Purpose: To document the rate and outcome of trastuzumab-associated cardiac dysfunction in patients following 1 or 2 years of adjuvant therapy. Patients and Methods: The Herceptin Adjuvant (HERA) trial is a three-arm, randomized trial comparing 2 years or 1 year of trastuzumab with observation in 5,102 patients with human epidermal growth factor receptor 2 (HER2) -positive early-stage breast cancer. Cardiac function was closely monitored. Eligible patients had left ventricular ejection fraction (LVEF) ≥ 55% at study entry following neoadjuvant chemotherapy with or without radiotherapy. This 8-year median follow-up analysis considered patients randomly assigned to 2 years or 1 year of trastuzumab or observation. Results: The as-treated safety population for 2 years of trastuzumab (n = 1,673), 1 year of trastuzumab (n = 1,682), and observation (n = 1,744) is reported. Cardiac adverse events leading to discontinuation of trastuzumab occurred in 9.4% of patients in the 2-year arm and 5.2% of patients in the 1-year arm. Cardiac death, severe congestive heart failure (CHF), and confirmed significant LVEF decrease remained low in all three arms. The incidence of severe CHF (0.8%, 0.8%, and 0.0%, respectively) and confirmed significant LVEF decrease (7.2%, 4.1%, and 0.9%, respectively) was significantly higher in the 2-year and 1-year trastuzumab arms compared with the observation arm. Severe CHF was the same for 2-year and 1-year trastuzumab. Of patients with confirmed LVEF decrease receiving 2-year trastuzumab, 87.5% reached acute recovery. Of patients with confirmed LVEF decrease receiving 1-year trastuzumab, 81.2% reached acute recovery. Conclusion: Long-term assessment at 8-year median follow-up confirms the low incidence of cardiac events for trastuzumab given sequentially after chemotherapy and radiotherapy, and cardiac events were reversible in the vast majority of patients.

Original languageEnglish
Pages (from-to)2159-2165
Number of pages7
JournalJournal of Clinical Oncology
Volume32
Issue number20
DOIs
Publication statusPublished - Jul 10 2014

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Stroke Volume
Observation
Heart Failure
Trastuzumab
Radiotherapy
Drug Therapy
Incidence
Breast Neoplasms
Safety
Population
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

De Azambuja, E., Procter, M. J., Van Veldhuisen, D. J., Agbor-Tarh, D., Metzger-Filho, O., Steinseifer, J., ... Suter, T. M. (2014). Trastuzumab-associated cardiac events at 8 years of median follow-up in the herceptin adjuvant trial (BIG 1-01). Journal of Clinical Oncology, 32(20), 2159-2165. https://doi.org/10.1200/JCO.2013.53.9288

Trastuzumab-associated cardiac events at 8 years of median follow-up in the herceptin adjuvant trial (BIG 1-01). / De Azambuja, Evandro; Procter, Marion J.; Van Veldhuisen, Dirk J.; Agbor-Tarh, Dominique; Metzger-Filho, Otto; Steinseifer, Jutta; Untch, Michael; Smith, Ian E.; Gianni, Luca; Baselga, Jose; Jackisch, Christian; Cameron, David A.; Bell, Richard; Leyland-Jones, Brian; Dowsett, Mitch; Gelber, Richard D.; Piccart-Gebhart, Martine J.; Suter, Thomas M.

In: Journal of Clinical Oncology, Vol. 32, No. 20, 10.07.2014, p. 2159-2165.

Research output: Contribution to journalArticle

De Azambuja, E, Procter, MJ, Van Veldhuisen, DJ, Agbor-Tarh, D, Metzger-Filho, O, Steinseifer, J, Untch, M, Smith, IE, Gianni, L, Baselga, J, Jackisch, C, Cameron, DA, Bell, R, Leyland-Jones, B, Dowsett, M, Gelber, RD, Piccart-Gebhart, MJ & Suter, TM 2014, 'Trastuzumab-associated cardiac events at 8 years of median follow-up in the herceptin adjuvant trial (BIG 1-01)', Journal of Clinical Oncology, vol. 32, no. 20, pp. 2159-2165. https://doi.org/10.1200/JCO.2013.53.9288
De Azambuja E, Procter MJ, Van Veldhuisen DJ, Agbor-Tarh D, Metzger-Filho O, Steinseifer J et al. Trastuzumab-associated cardiac events at 8 years of median follow-up in the herceptin adjuvant trial (BIG 1-01). Journal of Clinical Oncology. 2014 Jul 10;32(20):2159-2165. https://doi.org/10.1200/JCO.2013.53.9288
De Azambuja, Evandro ; Procter, Marion J. ; Van Veldhuisen, Dirk J. ; Agbor-Tarh, Dominique ; Metzger-Filho, Otto ; Steinseifer, Jutta ; Untch, Michael ; Smith, Ian E. ; Gianni, Luca ; Baselga, Jose ; Jackisch, Christian ; Cameron, David A. ; Bell, Richard ; Leyland-Jones, Brian ; Dowsett, Mitch ; Gelber, Richard D. ; Piccart-Gebhart, Martine J. ; Suter, Thomas M. / Trastuzumab-associated cardiac events at 8 years of median follow-up in the herceptin adjuvant trial (BIG 1-01). In: Journal of Clinical Oncology. 2014 ; Vol. 32, No. 20. pp. 2159-2165.
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abstract = "Purpose: To document the rate and outcome of trastuzumab-associated cardiac dysfunction in patients following 1 or 2 years of adjuvant therapy. Patients and Methods: The Herceptin Adjuvant (HERA) trial is a three-arm, randomized trial comparing 2 years or 1 year of trastuzumab with observation in 5,102 patients with human epidermal growth factor receptor 2 (HER2) -positive early-stage breast cancer. Cardiac function was closely monitored. Eligible patients had left ventricular ejection fraction (LVEF) ≥ 55{\%} at study entry following neoadjuvant chemotherapy with or without radiotherapy. This 8-year median follow-up analysis considered patients randomly assigned to 2 years or 1 year of trastuzumab or observation. Results: The as-treated safety population for 2 years of trastuzumab (n = 1,673), 1 year of trastuzumab (n = 1,682), and observation (n = 1,744) is reported. Cardiac adverse events leading to discontinuation of trastuzumab occurred in 9.4{\%} of patients in the 2-year arm and 5.2{\%} of patients in the 1-year arm. Cardiac death, severe congestive heart failure (CHF), and confirmed significant LVEF decrease remained low in all three arms. The incidence of severe CHF (0.8{\%}, 0.8{\%}, and 0.0{\%}, respectively) and confirmed significant LVEF decrease (7.2{\%}, 4.1{\%}, and 0.9{\%}, respectively) was significantly higher in the 2-year and 1-year trastuzumab arms compared with the observation arm. Severe CHF was the same for 2-year and 1-year trastuzumab. Of patients with confirmed LVEF decrease receiving 2-year trastuzumab, 87.5{\%} reached acute recovery. Of patients with confirmed LVEF decrease receiving 1-year trastuzumab, 81.2{\%} reached acute recovery. Conclusion: Long-term assessment at 8-year median follow-up confirms the low incidence of cardiac events for trastuzumab given sequentially after chemotherapy and radiotherapy, and cardiac events were reversible in the vast majority of patients.",
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T1 - Trastuzumab-associated cardiac events at 8 years of median follow-up in the herceptin adjuvant trial (BIG 1-01)

AU - De Azambuja, Evandro

AU - Procter, Marion J.

AU - Van Veldhuisen, Dirk J.

AU - Agbor-Tarh, Dominique

AU - Metzger-Filho, Otto

AU - Steinseifer, Jutta

AU - Untch, Michael

AU - Smith, Ian E.

AU - Gianni, Luca

AU - Baselga, Jose

AU - Jackisch, Christian

AU - Cameron, David A.

AU - Bell, Richard

AU - Leyland-Jones, Brian

AU - Dowsett, Mitch

AU - Gelber, Richard D.

AU - Piccart-Gebhart, Martine J.

AU - Suter, Thomas M.

PY - 2014/7/10

Y1 - 2014/7/10

N2 - Purpose: To document the rate and outcome of trastuzumab-associated cardiac dysfunction in patients following 1 or 2 years of adjuvant therapy. Patients and Methods: The Herceptin Adjuvant (HERA) trial is a three-arm, randomized trial comparing 2 years or 1 year of trastuzumab with observation in 5,102 patients with human epidermal growth factor receptor 2 (HER2) -positive early-stage breast cancer. Cardiac function was closely monitored. Eligible patients had left ventricular ejection fraction (LVEF) ≥ 55% at study entry following neoadjuvant chemotherapy with or without radiotherapy. This 8-year median follow-up analysis considered patients randomly assigned to 2 years or 1 year of trastuzumab or observation. Results: The as-treated safety population for 2 years of trastuzumab (n = 1,673), 1 year of trastuzumab (n = 1,682), and observation (n = 1,744) is reported. Cardiac adverse events leading to discontinuation of trastuzumab occurred in 9.4% of patients in the 2-year arm and 5.2% of patients in the 1-year arm. Cardiac death, severe congestive heart failure (CHF), and confirmed significant LVEF decrease remained low in all three arms. The incidence of severe CHF (0.8%, 0.8%, and 0.0%, respectively) and confirmed significant LVEF decrease (7.2%, 4.1%, and 0.9%, respectively) was significantly higher in the 2-year and 1-year trastuzumab arms compared with the observation arm. Severe CHF was the same for 2-year and 1-year trastuzumab. Of patients with confirmed LVEF decrease receiving 2-year trastuzumab, 87.5% reached acute recovery. Of patients with confirmed LVEF decrease receiving 1-year trastuzumab, 81.2% reached acute recovery. Conclusion: Long-term assessment at 8-year median follow-up confirms the low incidence of cardiac events for trastuzumab given sequentially after chemotherapy and radiotherapy, and cardiac events were reversible in the vast majority of patients.

AB - Purpose: To document the rate and outcome of trastuzumab-associated cardiac dysfunction in patients following 1 or 2 years of adjuvant therapy. Patients and Methods: The Herceptin Adjuvant (HERA) trial is a three-arm, randomized trial comparing 2 years or 1 year of trastuzumab with observation in 5,102 patients with human epidermal growth factor receptor 2 (HER2) -positive early-stage breast cancer. Cardiac function was closely monitored. Eligible patients had left ventricular ejection fraction (LVEF) ≥ 55% at study entry following neoadjuvant chemotherapy with or without radiotherapy. This 8-year median follow-up analysis considered patients randomly assigned to 2 years or 1 year of trastuzumab or observation. Results: The as-treated safety population for 2 years of trastuzumab (n = 1,673), 1 year of trastuzumab (n = 1,682), and observation (n = 1,744) is reported. Cardiac adverse events leading to discontinuation of trastuzumab occurred in 9.4% of patients in the 2-year arm and 5.2% of patients in the 1-year arm. Cardiac death, severe congestive heart failure (CHF), and confirmed significant LVEF decrease remained low in all three arms. The incidence of severe CHF (0.8%, 0.8%, and 0.0%, respectively) and confirmed significant LVEF decrease (7.2%, 4.1%, and 0.9%, respectively) was significantly higher in the 2-year and 1-year trastuzumab arms compared with the observation arm. Severe CHF was the same for 2-year and 1-year trastuzumab. Of patients with confirmed LVEF decrease receiving 2-year trastuzumab, 87.5% reached acute recovery. Of patients with confirmed LVEF decrease receiving 1-year trastuzumab, 81.2% reached acute recovery. Conclusion: Long-term assessment at 8-year median follow-up confirms the low incidence of cardiac events for trastuzumab given sequentially after chemotherapy and radiotherapy, and cardiac events were reversible in the vast majority of patients.

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