A recent phase III clinical trial has demonstrated that administering trastuzumab and anthracyclines concurrently is not necessary to achieve a high rate of complete pathologic remission in HER2-positive breast cancer. Sequential treatments are equally effective.
Over-expression of Human epidermal growth factor receptor 2 (HER2) is linked to a poor prognosis. HER2 over-expression is found in 25-30 percent of breast cancers. Earlier research demonstrated that patients with HER2-positive breast cancer treated with trastuzumab and anthracyclines concurrently resulted in a high pathologic complete response rate. Nevertheless, there was some concern that the combination therapy was linked with an increased risk of cardiac toxicity. The current trial was used to determine if concurrent administration was necessary to achieve a high pathologic complete response rate or does sequential administration achieve the same results.
According to Aman Buzdar, MD, at The University of Texas MD Anderson Cancer Center in Houston and primary author of the current trial, “Findings show that high pathologic response rates were observed in both treatment groups with similar cardiac safety profiles in both arms of the trial.”
The current phase III trial had 280 women participating with operable HER2-positive invasive breast cancer at 36 centers across the United States. Participants were randomly assigned to sequential or concurrent therapy.
The sequential group received fluorouracil, epirubicin, and cyclophosphamide on day 1 of a 21-day cycle for four cycles followed by paclitaxel plus trastuzumab weekly for 12 weeks. The concurrent group received paclitaxel and trastuzumab weekly for 12 weeks. This was followed by fluorouracil, epirubicin, and cyclophosphamide on day 1 of a 21-day cycle with trastuzumab on days 1, 8, and 15 of the 21-day cycle for four cycles. Patients in both groups received 1 year of trastuzumab therapy.
Buzdar notes, “If a patient achieves complete pathological remission, we know from previous experience that more than 90% continue to remain free of their disease at longer follow-up.” Researchers report that complete pathologic remission was observed in 56.5 percent of patients who received sequential therapy and 54.2 percent who received concurrent therapy. The difference is not statistically significant.
Breast tumors were obtained during the trial to analyze genomic profiles to evaluate specific tumor characteristics associated with sensitivity and resistance to treatment. According to Kelly Hunt, MD, professor in MD Anderson’s Department of Surgical Oncology and co-principal investigator of the trial, if individuals can be identified that are most likely to have a pathologic complete response with therapy, the need for surgery may be reduced or even potentially eliminated.