Long-term cardiac safety analysis of NCCTG N9831 (Alliance) adjuvant trastuzumab trial

Pooja P. Advani, Karla V. Ballman, Travis J. Dockter, Gerardo Colon-Otero, Edith A. Perez

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Purpose Significant improvement in survival outcomes has been established with the addition of trastuzumab to adjuvant chemotherapy for human epidermal growth factor receptor 2 (HER2) 'positive early breast cancer treatment. However, trastuzumab may increase the risk of cardiac toxicity, and longterm evaluation of its incidence and risk factors are warranted. Methods NCCTG (Alliance) N9831 trial compared adjuvant doxorubicin and cyclophosphamide (AC) followed by either weekly paclitaxel (arm A); paclitaxel then trastuzumab (arm B); or paclitaxel plus trastuzumab followed by trastuzumab alone (arm C) in patients with HER2-positive breast cancer. Cumulative incidence of cardiac events (CE) and left ventricular ejection fraction (LVEF) were evaluated in 1,944 women who proceeded to post-AC therapy. Risk factors for trastuzumab-induced cardiac toxicity were identified by Cox regression models. Results The 6-year cumulative incidence of CE was 0.6% in arm A, 2.8% in arm B, and 3.4% in arm C. At a median follow-up of 9.2 years, only two additional CHF diagnoses (of 1,046 patients) occurred beyond our previously reported follow-up time of 3.75 years. LVEF recovered in the majority of the patients who developed CHF. There were two cardiac deaths in arm A and one each in arms B and C. Age of 60 years or older, registration LVEF less than 65%, and use of antihypertensive medications were associated with an increased risk of CE in arms B and C. Conclusion The cumulative incidence of CE at 6 years was slightly higher with the addition of trastuzumab; however, the late development of CE is infrequent. Trastuzumab (in the context of anthracyclineand taxane-based therapy) continues to have a favorable benefit-risk ratio.

Original languageEnglish (US)
Pages (from-to)581-587
Number of pages7
JournalJournal of Clinical Oncology
Volume34
Issue number6
DOIs
StatePublished - Feb 20 2016

Fingerprint

Safety
Paclitaxel
Stroke Volume
Incidence
Cyclophosphamide
Breast Neoplasms
Trastuzumab
Adjuvant Chemotherapy
Proportional Hazards Models
Doxorubicin
Antihypertensive Agents
Therapeutics
Odds Ratio
Survival
Cardiotoxicity
human ERBB2 protein

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Long-term cardiac safety analysis of NCCTG N9831 (Alliance) adjuvant trastuzumab trial. / Advani, Pooja P.; Ballman, Karla V.; Dockter, Travis J.; Colon-Otero, Gerardo; Perez, Edith A.

In: Journal of Clinical Oncology, Vol. 34, No. 6, 20.02.2016, p. 581-587.

Research output: Contribution to journalArticle

Advani, Pooja P. ; Ballman, Karla V. ; Dockter, Travis J. ; Colon-Otero, Gerardo ; Perez, Edith A. / Long-term cardiac safety analysis of NCCTG N9831 (Alliance) adjuvant trastuzumab trial. In: Journal of Clinical Oncology. 2016 ; Vol. 34, No. 6. pp. 581-587.
@article{52145adf82834023b14b5f3b71c3c1f3,
title = "Long-term cardiac safety analysis of NCCTG N9831 (Alliance) adjuvant trastuzumab trial",
abstract = "Purpose Significant improvement in survival outcomes has been established with the addition of trastuzumab to adjuvant chemotherapy for human epidermal growth factor receptor 2 (HER2) 'positive early breast cancer treatment. However, trastuzumab may increase the risk of cardiac toxicity, and longterm evaluation of its incidence and risk factors are warranted. Methods NCCTG (Alliance) N9831 trial compared adjuvant doxorubicin and cyclophosphamide (AC) followed by either weekly paclitaxel (arm A); paclitaxel then trastuzumab (arm B); or paclitaxel plus trastuzumab followed by trastuzumab alone (arm C) in patients with HER2-positive breast cancer. Cumulative incidence of cardiac events (CE) and left ventricular ejection fraction (LVEF) were evaluated in 1,944 women who proceeded to post-AC therapy. Risk factors for trastuzumab-induced cardiac toxicity were identified by Cox regression models. Results The 6-year cumulative incidence of CE was 0.6{\%} in arm A, 2.8{\%} in arm B, and 3.4{\%} in arm C. At a median follow-up of 9.2 years, only two additional CHF diagnoses (of 1,046 patients) occurred beyond our previously reported follow-up time of 3.75 years. LVEF recovered in the majority of the patients who developed CHF. There were two cardiac deaths in arm A and one each in arms B and C. Age of 60 years or older, registration LVEF less than 65{\%}, and use of antihypertensive medications were associated with an increased risk of CE in arms B and C. Conclusion The cumulative incidence of CE at 6 years was slightly higher with the addition of trastuzumab; however, the late development of CE is infrequent. Trastuzumab (in the context of anthracyclineand taxane-based therapy) continues to have a favorable benefit-risk ratio.",
author = "Advani, {Pooja P.} and Ballman, {Karla V.} and Dockter, {Travis J.} and Gerardo Colon-Otero and Perez, {Edith A.}",
year = "2016",
month = "2",
day = "20",
doi = "10.1200/JCO.2015.61.8413",
language = "English (US)",
volume = "34",
pages = "581--587",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "6",

}

TY - JOUR

T1 - Long-term cardiac safety analysis of NCCTG N9831 (Alliance) adjuvant trastuzumab trial

AU - Advani, Pooja P.

AU - Ballman, Karla V.

AU - Dockter, Travis J.

AU - Colon-Otero, Gerardo

AU - Perez, Edith A.

PY - 2016/2/20

Y1 - 2016/2/20

N2 - Purpose Significant improvement in survival outcomes has been established with the addition of trastuzumab to adjuvant chemotherapy for human epidermal growth factor receptor 2 (HER2) 'positive early breast cancer treatment. However, trastuzumab may increase the risk of cardiac toxicity, and longterm evaluation of its incidence and risk factors are warranted. Methods NCCTG (Alliance) N9831 trial compared adjuvant doxorubicin and cyclophosphamide (AC) followed by either weekly paclitaxel (arm A); paclitaxel then trastuzumab (arm B); or paclitaxel plus trastuzumab followed by trastuzumab alone (arm C) in patients with HER2-positive breast cancer. Cumulative incidence of cardiac events (CE) and left ventricular ejection fraction (LVEF) were evaluated in 1,944 women who proceeded to post-AC therapy. Risk factors for trastuzumab-induced cardiac toxicity were identified by Cox regression models. Results The 6-year cumulative incidence of CE was 0.6% in arm A, 2.8% in arm B, and 3.4% in arm C. At a median follow-up of 9.2 years, only two additional CHF diagnoses (of 1,046 patients) occurred beyond our previously reported follow-up time of 3.75 years. LVEF recovered in the majority of the patients who developed CHF. There were two cardiac deaths in arm A and one each in arms B and C. Age of 60 years or older, registration LVEF less than 65%, and use of antihypertensive medications were associated with an increased risk of CE in arms B and C. Conclusion The cumulative incidence of CE at 6 years was slightly higher with the addition of trastuzumab; however, the late development of CE is infrequent. Trastuzumab (in the context of anthracyclineand taxane-based therapy) continues to have a favorable benefit-risk ratio.

AB - Purpose Significant improvement in survival outcomes has been established with the addition of trastuzumab to adjuvant chemotherapy for human epidermal growth factor receptor 2 (HER2) 'positive early breast cancer treatment. However, trastuzumab may increase the risk of cardiac toxicity, and longterm evaluation of its incidence and risk factors are warranted. Methods NCCTG (Alliance) N9831 trial compared adjuvant doxorubicin and cyclophosphamide (AC) followed by either weekly paclitaxel (arm A); paclitaxel then trastuzumab (arm B); or paclitaxel plus trastuzumab followed by trastuzumab alone (arm C) in patients with HER2-positive breast cancer. Cumulative incidence of cardiac events (CE) and left ventricular ejection fraction (LVEF) were evaluated in 1,944 women who proceeded to post-AC therapy. Risk factors for trastuzumab-induced cardiac toxicity were identified by Cox regression models. Results The 6-year cumulative incidence of CE was 0.6% in arm A, 2.8% in arm B, and 3.4% in arm C. At a median follow-up of 9.2 years, only two additional CHF diagnoses (of 1,046 patients) occurred beyond our previously reported follow-up time of 3.75 years. LVEF recovered in the majority of the patients who developed CHF. There were two cardiac deaths in arm A and one each in arms B and C. Age of 60 years or older, registration LVEF less than 65%, and use of antihypertensive medications were associated with an increased risk of CE in arms B and C. Conclusion The cumulative incidence of CE at 6 years was slightly higher with the addition of trastuzumab; however, the late development of CE is infrequent. Trastuzumab (in the context of anthracyclineand taxane-based therapy) continues to have a favorable benefit-risk ratio.

UR - http://www.scopus.com/inward/record.url?scp=84964292383&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84964292383&partnerID=8YFLogxK

U2 - 10.1200/JCO.2015.61.8413

DO - 10.1200/JCO.2015.61.8413

M3 - Article

C2 - 26392097

AN - SCOPUS:84964292383

VL - 34

SP - 581

EP - 587

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 6

ER -