New studies start to pinpoint the best strategy for treating HER2-positive breast cancer before surgery and lay the groundwork for future clinical trials. 

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Drug Combo Tames HER2-Positive Breast Cancer

BY MELISSA WEBER
PUBLISHED THURSDAY, DECEMBER 9, 2010
Treatment for HER2-positive breast cancer turned a corner more than a decade ago with the approval of Herceptin (trastuzumab). More recently, another successful drug called Tykerb (lapatinib) hit the market. The question then became whether Herceptin, Tykerb or a combination of the two would be most effective in stifling the aggressive disease. Two studies presented at the San Antonio Breast Cancer Symposium offer some clues.

In the first study, nicknamed NeoALTTO, a combination of Tykerb, Herceptin and the chemotherapy drug Taxol (paclitaxel) outdid either targeted agent alone. Among 455 patients with HER2-positive breast cancer, giving the three-drug combo before surgery—known as neoadjuvant therapy—resulted in half of patients seeing cancer cells disappear completely in the breast at the time of surgery. The same pathological complete response was seen in only 30 percent of women receiving Herceptin alone, and 25 percent for Tykerb alone. Serious side effects were more common in the Tykerb-alone arm and included diarrhea, liver function problems, low white blood cell counts and rash. Although heart damage has been associated with HER2-targeted drugs, no patients experienced toxic effects to the heart at the time of surgery, researchers reported.

Similarly, investigators in the GeparQuinto study wanted to know which of the HER2-targeted drugs was more effective when given before surgery. In a head-to-head comparison, 620 women with HER2-positive disease received chemotherapy (epirubicin and cyclophosphamide followed by Taxotere [docetaxel]) plus either Herceptin or Tykerb. Like the NeoALTTO results, Herceptin edged out Tykerb when added to chemotherapy. No cancer cells were detected in the breast or lymph nodes at the time of surgery in 31 percent of patients on Herceptin compared with 22 percent receiving Tykerb. Serious cases of diarrhea and low white blood cell counts were seen in the Tykerb arm of the study.

Investigators of both studies will follow patients to see whether the absence of cancer cells at the time of surgery results in longer survival.

The HER2-targeted drug combo also works in combating advanced breast cancer. Last year in San Antonio, researchers reported that combining Herceptin and Tykerb helped women with heavily pretreated metastatic disease live approximately 4.5 months longer than Tykerb alone.

Excessive amounts of the HER2 protein cause cancer cells to grow more rapidly—a scenario associated with 20 to 25 percent of all breast cancers. Herceptin, approved for both early-stage and advanced cancers, targets the HER2 protein on the outside of cancer cells. Tykerb, currently approved only for advanced HER2-positive breast cancer, enters the cancer cell and blocks HER2—as well as growth signals from another protein called HER1—from inside the cell. Combining the two drugs could essentially knock out the cancer cell with a double blow.

While the studies were very encouraging, they’re not ready for use outside a clinical trial, said Eric Winer, MD, chief of the division of women’s cancers at Dana-Farber Cancer Institute in Boston. “We’ve been misled too often with early results. And while on the one hand we want to bring the best treatments to people as soon as possible, on the other hand, we have to have some greater assurance that they’re really having a meaningful effect.” 

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