Herceptin or Herceptin Combination May Be Most Effective Before Surgery

Breast Cancer News
March 14, 2012
Michael J. Formica, MS, MA, EdM
Reviewed By: 
Harry D. Bear, MD, PhD

Two studies, published together in The Lancet, show that trastuzumab (Herceptin) or trastuzumab plus lapatinib (Tykerb) given with chemotherapy before surgery improve pathologic complete response in early-stage and locally advanced HER2 positive breast cancer.

Pathologic complete response means tests after surgery find no cancer cells in breast tissue or lymph nodes. It is an endpoint, or goal, of clinical trials that study neoadjuvant treatment (treatment before surgery).

Final results from the NeoALTTO trial confirm the study’s earlier findings that trastuzumab and lapatinib, given before surgery with the chemotherapy medicine paclitaxel (Taxol), had more benefit than paclitaxel and trastuzumab or lapatinib alone.

The GeparQuinto study showed pathologic complete response modestly increased in cancers treated with cyclophosphamide (Cytoxan) and epirubicin (Ellence) plus trastuzumab followed by docetaxel (Taxotere) plus trastuzumab, over those treated with the same medicines combined with lapatinib rather than trastuzumab.


Reason for the Studies


HER proteins regulate cell growth, as well as other cell functions. When there is too much HER2 protein, breast cancer cells grow more rapidly and behave more aggressively. Both trastuzumab and lapatinib target the HER2 protein, interrupting this uncontrolled cell growth in different ways.

Researchers in the NeoALTTO trial wanted to consider the impact of combining these two medicines with docetaxel as a treatment before surgery. In the GeparQuinto study, researchers looked at the effectiveness and safety of combining lapatinib or trastuzumab with epirubicin and cyclophosphamide, followed by docetaxel before surgery.


Structure and Results of the Studies


NeoALTTO researchers randomly assigned 455 women with early-stage or locally advanced HER2 positive breast cancer to receive one of three treatments:

  • Group 1 received lapatinib for six weeks, followed by lapatinib plus paclitaxel for 12 weeks
  • Group 2 got trastuzumab for six weeks, followed by trastuzumab plus paclitaxel for 12 weeks
  • Group 3 received lapatinib plus trastuzumab for six weeks, followed by lapatinib plus trastuzumab and paclitaxel for 12 weeks

After surgery, each group received three cycles of fluorouracil-epirubicin-cyclophosphamide (FEC) chemotherapy, for a total of 52 weeks of their assigned HER2-targeted therapy.

Final results showed 51.3 percent of women who received trastuzumab and lapatinib in combination with paclitaxel had a pathologic complete response, compared to 24.7 percent of those who received lapatinib plus paclitaxel, and 29.5 percent of those given trastuzumab plus paclitaxel. This difference was statistically significant, meaning it was unlikely to have occurred by chance, and suggests the combination of these medicines is a more effective treatment than either of them alone.

In the GeparQuinto study, 620 women with early-stage and locally advanced HER2 positive breast cancer were randomly assigned to receive 12 weeks of epirubicin and cyclophosphamide followed by 12 weeks of docetaxel; either trastuzumab or lapatinib was given throughout chemotherapy treatment. Both groups then received that same combination of docetaxel and trastuzumab or docetaxel and lapatinib for an additional 12 weeks.

Researchers found pathologic complete response was 30.3 percent for women who received trastuzumab before surgery, and 22.7 percent in those who received lapatinib. This suggests trastuzumab, when combined with these chemotherapy medicines, is the more effective of the two HER2-targeting treatments.

In the GeparQuinto study, severe diarrhea was more common in women who got lapatinib. Heart problems, a side effect of both medicines, were not seen in either study.


What These Studies Mean for You


If you have been recently diagnosed with HER2 positive breast cancer and have not yet had surgery, you may want to talk with your care team about whether neoadjuvant treatment is right for you. Chemotherapy combined with HER2-targeted therapy may change the kind of surgery you need.

Learn more about NeoALTTO and GeparQuinto.

Untch, M., et. al. Lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy (GeparQuinto, GBG 44): a randomized phase 3 trial. The Lancet Oncology, 13(2), February 2012.

Baselga, J., et. al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomized, open-label, multicentre, phase 3 trial. The Lancet, 379(9816), February 2012.

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