MedicalResearch.com Interview with:
Dr. Kelly K. Hunt, M.D., F.A.C.S.
Professor, Department of Surgical Oncology, Division of Surgery
Chief, Breast Surgical Oncology Section, Department of Surgical Oncology
The University of Texas MD Anderson Cancer Center, Houston, TX
MedicalResearch.com: What are the main findings of the study?
Dr. Hunt: The primary endpoint of the Z1041 trial was the proportion of patients who had pathological complete response in the breast, defined as the percentage of women who started the neoadjuvant treatment with no histological evidence of disease in the breast at surgery. We found that high pathologic response rates were observed in both treatment groups with similar cardiac safety profiles in both arms of the trial. Specifically, 56.5% of patients in the sequential group (fluorouracil, epirubicin and cyclophosphamide on day one of a 21-day cycle for four cycles followed by paclitaxel plus trastuzumab weekly for 12 weeks) had a complete pathological response versus 54.2% of the patients who received the concurrent regimen (paclitaxel and trastuzumab weekly for 12 weeks followed by fluorouracil, epirubicin and cyclophosphamide on day one of a 21-day cycle with trastuzumab on days one, eight and 15 of the 21-day cycle for four cycles). The difference in pathologic complete response rates between the treatment arms was not statistically significant. Cardiac safety was a secondary endpoint of the trial and we found that both regimens had acceptable cardiac safety profiles.
MedicalResearch.com: Were any of the findings unexpected?
Dr. Hunt: Based on results of previous trials, including a study performed at MD Anderson Cancer Center which was the basis for the current trial, we expected that the pathologic complete response rates would be higher in those patients who received the concurrent regimen where they received trastuzumab concurrently with both anthracyclines and taxanes in the neoadjuvant setting. In fact we found that similar high pathologic response rates were achieved whether the trastuzumab was delivered concurrently or sequentially with the anthracycline regimen.
MedicalResearch.com: What should clinicians and patients take away from your report?
Dr. Hunt: The take-home message is that concurrent administration of trastuzumab with anthracyclines does not provide additional benefit in terms of pathologic complete response rates in the neoadjuvant setting and therefore is not warranted. Therefore clinicians can avoid this concurrent regimen and alleviate some of the concerns about cardiac toxicity.
The standard chemotherapy agents utilized in this trial provided significant response in HER-2-positive breast cancer and the rates of pathologic complete response are similar to those seen with newer agents being evaluated in the neoadjuvant setting.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Dr. Hunt: Future trials will be focused on which patients can be treated with a standard regimen like that utilized in the Z1041 trial and avoid the cost and toxicity of additional agents. We are currently utilizing genomic studies to evaluate which tumors are most likely to respond to this regimen and which will be resistant. In addition, future studies will focus on which patients may benefit from the newer biologic therapies without the need for chemotherapy.
Fluorouracil, epirubicin, and cyclophosphamide (FEC-75) followed by paclitaxel plus trastuzumab versus paclitaxel plus trastuzumab followed by FEC-75 plus trastuzumab as neoadjuvant treatment for patients with HER2-positive breast cancer (Z1041): a randomised, controlled, phase 3 trial
Prof Aman U Buzdar MD,Prof Vera J Suman PhD,Prof Funda Meric-Bernstam MD,Prof A Marilyn Leitch MD,Prof Matthew J Ellis FRCP,Judy C Boughey MD,Gary Unzeitig MD,Prof Melanie Royce MD,Linda M McCall MS,Prof Michael S Ewer MD,Prof Kelly K Hunt MD,on behalf of the American College of Surgeons Oncology Group investigators
The Lancet Oncology – 13 November 2013