Pilot trial of paclitaxel-trastuzumab adjuvant therapy for early stage breast cancer

A trial of the ECOG-ACRIN cancer research group (E2198)

Bryan P. Schneider, Anne O'Neill, Fei Shen, George W. Sledge, Ann D. Thor, Stephen P. Kahanic, Paul J. Zander, Nancy E. Davidson

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Blockade of human epidermal growth factor receptor type 2 (HER2) has dramatically improved outcome for patients with HER2-positive breast cancer. Trastuzumab, an anti-HER2 monoclonal antibody, has previously demonstrated improvement in overall survival (OS) in patients with metastatic and early stage HER2-positive breast cancer. However, trastuzumab can cause congestive heart failure (CHF) with an increased frequency for patients who have also received an anthracycline. The current trial was designed to evaluate the impact of the duration of trastuzumab on CHF.Methods:E2198 included 227 eligible women with histologically confirmed stage II or IIIA HER2-positive breast cancer. The patients were randomised to receive 12 weeks of paclitaxel and trastuzumab followed by four cycles of doxorubicin and cyclophosphamide (abbreviated Arm) or the aforementioned treatment with additional 1 year of trastuzumab (conventional Arm). The primary end point was to evaluate the safety of this variable duration of trastuzumab therapy, particularly cardiac toxicity defined as CHF or left ventricular ejection fraction decrease >10%. Secondary end points included disease-free survival (DFS) and OS.Results:Compared with 12-week treatment with trastuzumab, 1 year of trastuzumab-based therapy did not increase the frequency or severity of cardiac toxicity: three patients on the abbreviated Arm and four on the conventional Arm experienced CHF. The 5-year DFS was 76% and 73% for the abbreviated and conventional Arms, respectively, with a hazard ratio (HR) of 1.3 (95% CI: 0.8-2.1; P=0.3). There was also no statistically significance difference in OS (HR, 1.4; P=0.3).Conclusions:Compared with 12 weeks of treatment, 1 year of treatment with trastuzumab did not significantly increase the risk of cardiac toxicity. Although not powered for efficacy comparisons, the longer duration of trastuzumab therapy did not demonstrate a signal for marked superiority.

Original languageEnglish (US)
Pages (from-to)1651-1657
Number of pages7
JournalBritish Journal of Cancer
Volume113
Issue number12
DOIs
StatePublished - Dec 22 2015

Fingerprint

Paclitaxel
Breast Neoplasms
Research
Neoplasms
Heart Failure
Therapeutics
Disease-Free Survival
Survival
Trastuzumab
Anthracyclines
Stroke Volume
Doxorubicin
Cyclophosphamide
Monoclonal Antibodies
Safety

Keywords

  • adjuvant trial
  • breast cancer
  • congestive heart failure
  • duration of therapy
  • HER2+
  • trastuzumab

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Pilot trial of paclitaxel-trastuzumab adjuvant therapy for early stage breast cancer : A trial of the ECOG-ACRIN cancer research group (E2198). / Schneider, Bryan P.; O'Neill, Anne; Shen, Fei; Sledge, George W.; Thor, Ann D.; Kahanic, Stephen P.; Zander, Paul J.; Davidson, Nancy E.

In: British Journal of Cancer, Vol. 113, No. 12, 22.12.2015, p. 1651-1657.

Research output: Contribution to journalArticle

Schneider, Bryan P. ; O'Neill, Anne ; Shen, Fei ; Sledge, George W. ; Thor, Ann D. ; Kahanic, Stephen P. ; Zander, Paul J. ; Davidson, Nancy E. / Pilot trial of paclitaxel-trastuzumab adjuvant therapy for early stage breast cancer : A trial of the ECOG-ACRIN cancer research group (E2198). In: British Journal of Cancer. 2015 ; Vol. 113, No. 12. pp. 1651-1657.
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abstract = "Blockade of human epidermal growth factor receptor type 2 (HER2) has dramatically improved outcome for patients with HER2-positive breast cancer. Trastuzumab, an anti-HER2 monoclonal antibody, has previously demonstrated improvement in overall survival (OS) in patients with metastatic and early stage HER2-positive breast cancer. However, trastuzumab can cause congestive heart failure (CHF) with an increased frequency for patients who have also received an anthracycline. The current trial was designed to evaluate the impact of the duration of trastuzumab on CHF.Methods:E2198 included 227 eligible women with histologically confirmed stage II or IIIA HER2-positive breast cancer. The patients were randomised to receive 12 weeks of paclitaxel and trastuzumab followed by four cycles of doxorubicin and cyclophosphamide (abbreviated Arm) or the aforementioned treatment with additional 1 year of trastuzumab (conventional Arm). The primary end point was to evaluate the safety of this variable duration of trastuzumab therapy, particularly cardiac toxicity defined as CHF or left ventricular ejection fraction decrease >10{\%}. Secondary end points included disease-free survival (DFS) and OS.Results:Compared with 12-week treatment with trastuzumab, 1 year of trastuzumab-based therapy did not increase the frequency or severity of cardiac toxicity: three patients on the abbreviated Arm and four on the conventional Arm experienced CHF. The 5-year DFS was 76{\%} and 73{\%} for the abbreviated and conventional Arms, respectively, with a hazard ratio (HR) of 1.3 (95{\%} CI: 0.8-2.1; P=0.3). There was also no statistically significance difference in OS (HR, 1.4; P=0.3).Conclusions:Compared with 12 weeks of treatment, 1 year of treatment with trastuzumab did not significantly increase the risk of cardiac toxicity. Although not powered for efficacy comparisons, the longer duration of trastuzumab therapy did not demonstrate a signal for marked superiority.",
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