Giving trastuzumab and anthracyclines concurrently is not necessary to achieve a high rate of complete pathologic remission in HER2-positive breast cancer, according to new research. The results of a recent phase III clinical trial show that administering the treatments sequentially is equally effective.
HER2 overexpression is associated with a poor prognosis, and is found in 25% to 30% of breast cancers. A previous study showed that patients with HER2-positive breast cancer who were treated with trastuzumab and anthracyclines concurrently had a high pathologic complete response rate. However, there was concern that this combination therapy was associated with an increased risk of cardiac toxicity.
The current trial addressed whether simultaneous administration of anthracyclines with trastuzumab was necessary for a high pathologic complete response rate, or if sequential administration could achieve similar results.
“Findings show that high pathologic response rates were observed in both treatment groups with similar cardiac safety profiles in both arms of the trial,” said primary author Aman Buzdar, MD, of The University of Texas MD Anderson Cancer Center in Houston.
This randomized phase III trial involved 280 women with operable HER2 positive invasive breast cancer at 36 centers across the United States. Patients were randomly assigned to either a sequential or concurrent treatment regimen.
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.
The primary end point of the trial was the proportion of patients who had complete pathologic remission. “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,” Buzdar said.
Complete pathologic remission was observed in 56.5% of patients who received the sequential regimen and 54.2% of the patients who received the concurrent regimen. This difference was not significant. These findings were published in The Lancet Oncology (2013; doi:10.1016/S1470-2045(13)70502-3)
Researchers are now analyzing the genomic profiles of the breast tumors obtained during the trial to evaluate specific tumor characteristics associated with sensitivity and resistance to therapy.
Kelly Hunt, MD, professor in MD Anderson’s Department of Surgical Oncology and coprincipal investigator of the trial, said that if the patients most likely to have pathologic complete response with therapy can be identified, surgery can be reduced or potentially eliminated for these patients in the future.