Study Suggests Early Response to HER2-Positive Breast Cancer Therapy Could Equal Survival Advantage

Women with an aggressive type of breast cancer—one that has an increased amount of the HER2 protein—may soon have another option to treat the disease and remain cancer-free, thanks to data presented at the 36th annual San Antonio Breast Cancer Symposium in December.

About 20 to 25 percent of all breast cancers are HER2-positive, meaning they have a genetic irregularity that produces an abundance of the HER2 protein—a contributor to rapid cancer growth. Drugs designed to block HER2's activity can effectively lower the risk of cancer spreading. Two approved drugs, Herceptin (trastuzumab) and Tykerb (lapatinib), target HER2 in different ways. Herceptin works to block HER2 on the cancer cell surface, while Tykerb works to block the protein from within the cell.

The NeoALTTO study compared three HER2-targeted treatment regimens: Herceptin plus paclitaxel, Tykerb plus paclitaxel, and a combination of the two plus paclitaxel. In 2010, the investigators announced they had observed a pathologic complete response (pCR) in 51.3 percent of participants taking the combination—about twice the rate of response seen in those taking the drugs individually.

Patients who experience a pCR tend to have fewer recurrences and deaths from breast cancer. Therefore, a pCR is considered an interim or surrogate endpoint of scientific analysis, meaning it can be used as a measurement in a clinical trial and the drug approval process, but the results must be supported by later research to maintain approval. By using pCR as an endpoint, researchers hope to get promising experimental therapies to patients faster.

In the NeoALTTO study, the investigators wanted to confirm if the benefits they had observed earlier might translate to long-term survival advantages.

Martine Piccart-Gebhart, chairwoman of the Breast International Group in Brussels, Belgium, reported that the participants who had achieved pCR, at a median follow-up of four years, had also experienced significantly improved event-free survival and overall survival, with even better results in women who had hormone-negative breast cancer. She cautioned, however, that the data regarding whether combination is better than Herceptin or Tykerb alone were not only premature but also not the objective of the study. That question will be answered by the much larger ALTTO study where all patients were treated after surgery using the same treatment arms, and that study is expected to be reported at the American Society of Clinical Oncology meeting in June 2014. Still, they pointed to a trend, and they confirmed the assumption of many researchers that early benefits of a therapy can translate to long-term effectiveness.