Kelly K. Hunt, MD Department of Breast Surgical Oncology The University of Texas MD Anderson Cancer Center Houston

Disease-Free and Overall Survival Among Patients With Operable HER2-Positive Breast Cancer Treated With Sequential vs Concurrent Chemotherapy

MedicalResearch.com Interview with:

Kelly K. Hunt, MD Department of Breast Surgical Oncology The University of Texas MD Anderson Cancer Center Houston

Dr. Hunt

Kelly K. Hunt, MD
Department of Breast Surgical Oncology
The University of Texas MD Anderson Cancer Center
Houston

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We completed a neoadjuvant trial at MD Anderson Cancer Center and published the results in 2005 demonstrating that trastuzumab delivered in combination with anthracycline and taxane based chemotherapy resulted in pathologic complete response rates of up to 60% in patients with HER-2 positive breast cancer. This was a single institutions study and there was concern about cardiac toxicity when using anthracyclines and trastuzumab concurrently.

We therefore worked with the NCI cooperative groups, the American College of surgeons oncology group (ACOSOG), to design the ACOSOG Z1041 trial. This trial compared to different regimens in the neoadjuvant setting, one regimen utilizing concurrent anthracycline and taxanes based chemotherapy with trastuzumab and the other regimen utilizing concurrent taxanes with trastuzumab but the anthracycline was delivered in a sequential fashion.

The primary end point of the trial was pathologic complete response rates in the breast.

The results from this primary end point were published in the Lancet Oncology in 2013 and showed that the pathologic complete response rates were the same with the 2 different regimens. This was important since patients could be assured of similar efficacy without the potential added toxicity of delivering anthracyclines and trastuzumab together.

The current publication is a report of the disease-free and overall survival rates from the Z1041 trial. Several studies have shown an association between pathologic complete response rates and survival. The current study shows that there is no difference in survival rates between the 2 different regimens. So once again there is an association between pathologic complete response and survival and it is not important that the anthracycline and trastuzumab are given concurrently in order to achieve these high pathologic complete response rates and improve survival rates.

MedicalResearch.com: What should readers take away from your report?

Response: Readers can take away the finding that disease-free and overall survival rates are quite high utilizing a neoadjuvant regimen of an anthracycline and a taxane in addition to trastuzumab. The anthracycline does not need to be delivered concurrently with trastuzumab and therefore this should lessen any concern regarding cardiac toxicity. This regimen results in high pathologic complete response rates (50%). Long-term survival rates are excellent in patients who achieve pathologic complete response with these neoadjuvant regimens. 

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: It will be important to study the role of additional therapies in the adjuvant setting for patients who do not achieve a pathologic complete response with standard chemotherapy (anthracycline, taxanes and trastuzumab). There are now several additional HER-2 targeted agents approved and the optimal use of these agents for patients with HER-2 positive breast cancer has yet to be defined. Studies should be designed that can assess the possibility of biologic therapies alone without the need for chemotherapy in this breast cancer subtype. Additional biomarkers are needed to identify patients with HER-2 positive breast cancer that may not need chemotherapy and therefore can avoid the toxicities associated with its administration.

MedicalResearch.com: Is there anything else you would like to add? 

Response: The neoadjuvant approach allows for increased surgical options for patients since the rate of pathologic complete response in the breast is so high. We also see eradication of lymph node metastases using these neoadjuvant approaches and therefore can potentially reduce the extent of nodal surgery that patients undergo as well.

I do not have any disclosures to report other than those that were published in the manuscript. There are node disclosures specifically related to this research study.

Citation:

Buzdar AU, Suman VJ, Meric-Bernstam F, et al. Disease-Free and Overall Survival Among Patients With Operable HER2-Positive Breast Cancer Treated With Sequential vs Concurrent ChemotherapyThe ACOSOG Z1041 (Alliance) Randomized Clinical Trial. JAMA Oncol. Published online September 06, 2018. doi:10.1001/jamaoncol.2018.3691 

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Last Updated on September 15, 2018 by Marie Benz MD FAAD