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Study Opens for HER2-Positive Patients

CancerWise - January 2008

By Darcy De Leon

Women newly diagnosed with HER2-positive breast cancer are being enrolled in a national clinical trial comparing the effectiveness and safety of different combinations of trastuzumab (Herceptin®) with standard chemotherapy before surgery.

Between 25% and 30% of breast cancers are known to overproduce the human epidermal growth factor receptor 2 (HER2), a protein that fuels growth and aggressiveness of the cancer. Trastuzumab is a drug designed to block the action of these receptors, but its use alone has shown only modest benefits.

Significance of study

The multi-center trial is based on a previous Phase III M. D. Anderson study of 42 patients. In that trial, 67% of patients treated with trastuzumab and standard chemotherapy experienced a complete disappearance of cancer within the breast and lymph nodes, compared to 25% of patients who received chemotherapy alone, says Funda Meric-Bernstam, M.D., an associate professor in M. D. Anderson's Department of Surgical Oncology and co-principal investigator on the current M. D. Anderson study.

Goal of study

"In the new study, we will determine how to best combine trastuzumab with standard chemotherapy," says Aman Buzdar, M.D., principal investigator on the national trial being conducted through the American College of Surgical Oncology Group and co-principal investigator on the M. D. Anderson trial.

“We know that giving FEC (fluorouracil, epirubicin and cyclophosphamide) and paclitaxel (Taxol®) with trastuzumab was highly effective in the previous clinical trial done at M. D. Anderson," Meric-Bernstam says. "This national study will determine whether giving FEC alone and then giving trastuzumab along with paclitaxel will be as effective as giving trastuzumab with both chemotherapy drug treatments (FEC and paclitaxel).The second objective of the trial is to determine whether the treatments reduce tumor size enough to allow for breast conservation."

Study description

The new study divides patients into two arms:

FEC/PAC and trastuzumab: Patients in this group will receive four cycles (12 weeks) of FEC, followed by weekly paclitaxel treatments for 12 weeks, along with weekly treatments of trastuzumab.

PAC and trastuzumab/FEC and trastuzumab: Patients in this group will receive weekly paclitaxel for 12 weeks plus weekly administration of trastuzumab, followed by four cycles (12 weeks) of FEC plus weekly trastuzumab treatments.

When treatment is complete, patients in both arms will be assessed and undergo surgery and radiation (if needed) to remove their tumors. Patients then will receive trastuzumab every three weeks for a total of 52 weeks.

Patients are treated for six months then followed by doctors every six months for five years, Meric-Bernstam says. Researchers hope to accrue 270 patients at multiple sites throughout the United States.


Patients in the Phase III M. D. Anderson trial, conducted between 2001 and 2003, were treated in two arms:

PAC/FEC: Participants received four cycles of paclitaxel followed by four cycles of FEC alone (25% of patients' tumors had a complete response).

PAC/FEC and trastuzumab: Participants received four cycles of paclitaxel followed by four cycles of FEC for 24 weeks, while receiving trastuzumab simultaneously (67% of patients' tumors had a complete response).

The U.S. Food and Drug Administration (FDA) approved trastuzumab in 1998 for treatment of metastatic breast cancer combined with chemotherapy. In 2006, the FDA expanded the approval for the use of trastuzumab to early stage estrogen receptor-positive (ER2-positive) breast cancer, in combination with other cancer drugs, after surgery (lumpectomy or mastectomy).

Possible side effects

In Buzdar's earlier study, none of the patients experienced heart failure. However, one of the major objectives of this larger study is to define the cardiac safety of this approach, he says.

Fever or neutropenia (low white blood cell count) also was experienced by a small percentage of patients, particularly among those on the trastuzumab arm of the trial.

"We don't have long-term cardiac safety data with the combination of FEC and trastuzumab," Meric-Bernstam adds. "FEC and PAC have side effects, and the combination with trastuzumab might amplify cardiotoxicity. But we will monitor patients closely."


Participants should have:

  • No cardiac problems
  • Breast cancer that is treatable by surgery
  • The HER2-positive gene
  • Not been treated previously
  • A tumor that is 2 centimeters or larger

One issue for potential participants to consider is whether the study treatment would be covered by their insurance companies.

"Not all insurance companies cover the treatment," Meric-Bernstam says. "Some insurance companies cover chemotherapy and trastuzumab individually, but not both together."

In this study, however, trastuzumab is being provided by the National Cancer Institute without charge to the patient, Buzdar says.

For more information about the study, also known as protocol Z1041, visit the ACSOG website. For more information about the study at M. D. Anderson, contact askMDAnderson at 1-877-632-6789.

M. D. Anderson resources:

© 2015 The University of Texas MD Anderson Cancer Center