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Effect of Early Trastuzumab Interruption on Recurrence-Free Survival in HER2-Positive Breast Cancer


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In a single-center analysis reported in a research letter in JAMA Oncology, Copeland-Halperin et al found that early trastuzumab interruption and interruption resulting in a cumulative trastuzumab dose ≤ 56 mg/kg were associated with significantly poorer recurrence-free survival in patients with HER2-positive breast cancer compared with continuous treatment.

Study Details

The study included data from 1,396 patients with HER2-positive breast cancer treated with trastuzumab at Memorial Sloan Kettering Cancer Center from 2004 to 2013. Early interruption was defined as a 6-week or longer interval between scheduled trastuzumab doses. Causes of interruption were categorized as cardiac (ie, asymptomatic left ventricular ejection fraction decline or heart failure) or noncardiac. The primary outcome measure was recurrence-free survival.

Key Findings

Among the 1,396 patients, treatment interruption occurred in 184 (13%), including in 124 for cardiotoxic effects (92 with left ventricular ejection fraction decline and 32 with heart failure) and in 60 for noncardiac causes.

After median follow-up of 6.0 years, invasive recurrence or death occurred in 44 (24%) of 184 patients in the interrupted group vs 153 (13%) of 1,212 in the continuous group (P < .001). On multivariate analysis adjusting for age, anthracycline use, cancer stage, estrogen/progesterone receptor status, hypertension, and diabetes, the adjusted hazard ratio for recurrence-free survival for the early interruption vs continuous groups was 1.56 (95% confidence interval [CI] = 1.10–2.21).

The adjusted hazard ratio was 1.47 (95% CI = 0.98–2.20) in the group with a cardiac interruption and 1.78 (95% CI = 1.03–3.08) in the group with a noncardiac interruption.

A total of 60 patients (33%) in the interrupted group vs none in the continuous group received a cumulative trastuzumab dose of ≤ 56 mg/kg (equivalent to ≤ 6 months of treatment). Among these patients, the adjusted hazard ratio was 1.96 (95% CI = 1.16–3.33). Among patients with interruption who received > 56 mg/kg, the adjusted hazard ratio was 1.39 (95% CI = 0.92–2.11).

The investigators stated, “This study demonstrates that patients with early trastuzumab interruption had poorer recurrence-free survival compared with patients receiving uninterrupted treatment…The most common cause for early interruption was cardiotoxic effects…highlighting the potential that such interruptions may adversely affect breast cancer outcomes. Given that most patients in this study were treated with anthracyclines, our findings may not be generalizable to patients receiving nonanthracycline treatment regimens. Recent studies suggest that asymptomatic left ventricular ejection fraction declines can safely be treated without interrupting trastuzumab when close cardiac monitoring and appropriate cardiac medications are instituted…Given that current clinical trial data are insufficient to support shortened durations of trastuzumab, ongoing collaboration between cardiologists and oncologists is needed to minimize treatment interruptions and allow patients with asymptomatic left ventricular ejection fraction decline to continue receiving [HER2]-targeted therapy.”

Anthony F. Yu, MD, of the Department of Medicine, Cardiology Service, Memorial Sloan Kettering Cancer Center, is the corresponding author for the JAMA Oncology article.

Disclosure: The study was funded by grants from the National Institutes of Health. For full disclosures of the study authors, visit jamanetwork.com.

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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