Understanding Optimal Timing of Trastuzumab in HER2+ Breast Cancer

By Annette M. Boyle /alert Contributor
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Several studies have demonstrated a significant increase in pathologic complete response in women with human epidermal growth factor receptor 2 positive (HER2+) breast cancer when trastuzumab is added to treatment with paclitaxel and fluorouracil, epirubicin and cyclophosphamide (FEC). But when trastuzumab should be added to generate the greatest benefit has remained a matter of continued debate.

A new study in JAMA Oncology finally answers the question: Is trastuzumab most effective when administered concurrently or sequentially?

Monitoring scan. Source: iStock

In short, the timing makes no difference in efficacy. Offering the therapy concurrently, however, avoids the cardiac toxicities associated with simultaneous delivery of HER2 therapy and anthracycline-based chemotherapy.

“The research also offers physicians definitive clinical guidance. Many have opted to treat with a more aggressive approach because the patient’s disease was a higher stage, or because of the woman’s young age. Our study confirms that for HER2+ breast cancer patients, less is more,” said corresponding author Kelly Hunt, MD, of the University of Texas MD Anderson Cancer Center in Houston.

Researchers conducted the ACOSOG Z1041 (Alliance) phase 3 trial at 36 US centers that enrolled 280 women between September 15, 2007 and December 15, 2011. Data collection stopped on October 15, 2017.

All patients had invasive, operable HER2+ breast cancer and were randomized to one of two arms. Women in arm 1 (sequential) received FEC every three weeks for 12 weeks, followed by paclitaxel and trastuzumab for 12 weeks. Women in arm 2 (concurrent) received paclitaxel with trastuzumab for 12 weeks followed by FEC every three weeks and weekly trastuzumab for 12 weeks.

After surgery, patients received trastuzumab every three weeks to reach a total of 52 weeks of treatment. Those with hormone receptor positive disease also received endocrine therapy and physicians had the option of adding radiotherapy.

The participants had a median age of 50 years, ranging from 28 to 76 years of age and 82.9% were white.

During the study, 22 women in the sequential group and 27 women in the concurrent group experienced disease events. With a median follow up of 5.1 years, the investigators determined that neither disease free survival nor overall survival differed between the arms. The two groups also had no significant difference in rates of pathologic complete response, according to an earlier report from the same trial.

The researchers concluded that “concurrent administration of trastuzumab with FEC was not found to offer additional clinical benefit and is not warranted.”