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6-Year Incidence of Cardiac Events in NCCTG N9831/Alliance Adjuvant Trastuzumab Trial

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Key Points

  • 6-year cumulative incidence of cardiac events was significantly higher in patients receiving trastuzumab.
  • Risk factors included greater age, lower baseline left-ventricular ejection fraction, and use of antihypertensive medication.

As reported in the Journal of Clinical Oncology by Advani et al, the cumulative incidence of cardiac events remained significantly higher at 6 years in breast cancer patients who received adjuvant trastuzumab (Herceptin) in the NCCTG N9831/Alliance trial. However, few new congestive heart failure cases were observed since the last update at 3.75 years.

Study Details

The NCCTG N9831/Alliance trial compared adjuvant doxorubicin and cyclophosphamide (AC) followed by 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. The current analysis involved 1,944 women who received post-AC therapy, including 664 in arm A, 710 in arm B, and 570 in arm C.

Cardiac Events and Congestive Heart Failure

The 6-year cumulative incidence of cardiac events was 0.6% in arm A, 2.8% in arm B (hazard ratio [HR] = 2.6, 95% confidence interval [CI] = 1.1–6.2, vs arm A), and 3.4% in arm C (HR = 3.4, 95% CI = 1.4–8.0, vs arm A). Symptomatic congestive heart failure occurred in 45 patients, consisting of 6 in arm A, 19 in arm B, and 20 in arm C. There were five additional congestive heart failure cases since the last reported follow-up at 3.75 years, consisting of three in arm A and two in arms B and C. Among all patients with congestive heart failure, left-ventricular ejection fraction recovered in 4 of 6 in arm A, 12 of 19 in arm B, and 12 of 20 in arm C. Cardiac death occurred in two patients in arm A and in one patient each in arms B and C.

Factors associated with increased risk of a cardiac event among patients receiving trastuzumab were age ≥ 60 years (HR = 3.2, P = .010), baseline left-ventricular ejection fraction of 50% to 54.9% (HR = 3.6, P = .020) or 55% to 64.9% (HR = 2.7, P =.009), and use of antihypertensive medications (HR = 2.4, P = .0148).

The investigators concluded: “The cumulative incidence of [cardiac events] at 6 years was slightly higher with the addition of trastuzumab; however, the late development of [cardiac events] is infrequent. Trastuzumab (in the context of anthracycline and taxane-based therapy) continues to have a favorable benefit-risk ratio.”

Edith A. Perez, MD, of Mayo Clinic, Jacksonville, is the corresponding author for the Journal of Clinical Oncology article.

The study was supported by National Cancer Institute awards. For full disclosures of the study authors, visit jco.ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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