Assessment of Cardiac Dysfunction in a Randomized Trial Comparing Doxorubicin and Cyclophosphamide Followed by Paclitaxel, With or Without Trastuzumab As Adjuvant Therapy in Node-Positive, Human Epidermal Growth Factor Receptor 2–Overexpressing Breast Cancer: NSABP B-31

Author:

Tan-Chiu Elizabeth1,Yothers Greg1,Romond Edward1,Geyer Charles E.1,Ewer Michael1,Keefe Deborah1,Shannon Richard P.1,Swain Sandra M.1,Brown Ann1,Fehrenbacher Louis1,Vogel Victor G.1,Seay Thomas E.1,Rastogi Priya1,Mamounas Eleftherios P.1,Wolmark Norman1,Bryant John1

Affiliation:

1. From the National Surgical Adjuvant Breast and Bowel Project (NSABP); NSABP Biostatistical Center, University of Pittsburgh; Allegheny General Hospital; University of Pittsburgh Cancer Institute, Breast Cancer Institute, and Magee Women's Hospital, Pittsburgh, PA; Cancer Research Network, Inc, Plantation, FL; University of Kentucky Markey Cancer Center, Lexington, KY; The University of Texas, M.D. Anderson Cancer Center, Houston, TX; Novartis Pharmaceutical Corporation, East Hanover, NJ; Cancer...

Abstract

Purpose Trastuzumab is effective in treating human epidermal growth factor receptor 2 (HER2) –positive breast cancer, but it increases frequency of cardiac dysfunction (CD) when used with or after anthracyclines. Patients and Methods National Surgical Adjuvant Breast and Bowel Project trial B-31 compared doxorubicin and cyclophosphamide (AC) followed by paclitaxel with AC followed by paclitaxel plus 52 weeks of trastuzumab beginning concurrently with paclitaxel in patients with node-positive, HER2-positive breast cancer. Initiation of trastuzumab required normal post-AC left ventricular ejection fraction (LVEF) on multiple-gated acquisition scan. If symptoms suggestive of congestive heart failure (CHF) developed, source documents were blindly reviewed by an independent panel of cardiologists to determine whether criteria were met for a cardiac event (CE), which was defined as New York Heart Association class III or IV CHF or possible/probable cardiac death. Frequencies of CEs were compared between arms. Results Among patients with normal post-AC LVEF who began post-AC treatment, five of 814 control patients subsequently had confirmed CEs (four CHFs and one cardiac death) compared with 31 of 850 trastuzumab-treated patients (31 CHFs and no cardiac deaths). The difference in cumulative incidence at 3 years was 3.3% (4.1% for trastuzumab-treated patients minus 0.8% for control patients; 95% CI, 1.7% to 4.9%). Twenty-seven of the 31 patients in the trastuzumab arm have been followed for ≥ 6 months after diagnosis of a CE; 26 were asymptomatic at last assessment, and 18 remained on cardiac medication. CHFs were more frequent in older patients and patients with marginal post-AC LVEF. Fourteen percent of patients discontinued trastuzumab because of asymptomatic decreases in LVEF; 4% discontinued trastuzumab because of symptomatic cardiotoxicity. Conclusion Administering trastuzumab with paclitaxel after AC increases incidence of CHF and lesser CD. Potential cardiotoxicity should be carefully considered when discussing benefits and risks of this therapy.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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