Concurrent Anthracyclines/Trastuzumab Offers No Added Benefit for HER2-Positive Breast Cancer in Neoadjuvant Setting

Concurrent administration of trastuzumab and anthracyclines resulted in a similar rate of pathologic complete response when compared to sequential administration in women with HER2-positive breast cancer, according to the results of the Z1041 trial published recently in Lancet Oncology.

Based on these results, clinicians should avoid the concurrent use of this regimen, alleviating some concerns about cardiac toxicity, according to the researchers.

“Previous studies have shown that giving trastuzumab and anthracyclines at the same time is effective at treating HER2-positive breast cancer and in the neoadjuvant setting this has resulted in very high pathologic complete response rates,” said study author Kelly K. Hunt, MD, of the department of surgical oncology at The University of Texas MD Anderson Cancer Center. “There has been concern that this combination can be associated with an increased risk of cardiac toxicity and, therefore, it was important to study the need for concurrent administration of anthracyclines and trastuzumab as compared with sequential administration.”

Hunt and colleagues from the American College of Surgeons Oncology Group conducted a randomized, phase III study of 282 women with HER2-positive breast cancer taken from 36 centers in the United States and Puerto Rico. Patients were assigned to sequential (n = 140) fluorouracil, epirubicin, and cyclophosphamide followed by paclitaxel/trastuzumab or the same regimen given concurrently (n = 142). The primary outcome was the percentage of patients achieving pathologic complete response in the intention-to-treat population.

Of the patients treated sequentially, 56.5% achieved a complete pathological response compared with 54.2% of patients receiving concurrent treatment.

“We found that high pathologic response rates were observed in both treatment groups with similar cardiac safety profiles in both arms of the trial,” Hunt said. “Based on results of previous trials we expected that the pathologic complete response rates would be higher in those patients who received the concurrent regimen where they had trastuzumab concurrently with both anthracyclines and taxanes.”

Neutropenia and fatigue were the most commonly occurring severe toxic effects. One patient on sequential therapy and four patients on concurrent therapy had a left ventricular ejection fraction that dropped below the institutional lower limit of normal at week 12. At week 24, this had occurred in nine patients on sequential treatment and six on concurrent.

“We found that the standard chemotherapy agents utilized in this trial provided significant response in HER2-positive breast cancer and the rates of pathologic complete response are similar to those seen with newer agents being evaluated in the neoadjuvant setting,” Hunt said. “The real challenge will be to determine which patients can be treated with a standard regimen like that utilized in the Z1041 trial and which patients may benefit from the newer biologic therapies with or without chemotherapy.”