Breast Cancer Strategy Uses Two Drugs Effectively

SAN ANTONIO, Dec. 16 -- A combination treatment -- attacking two separate breast cancer pathways -- is a "reasonable strategy" for some women with metastatic disease, researchers said here.

For women whose metastatic tumors are estrogen receptor-positive and HER2-positive, treatment with drugs targeting both can double disease-free survival after surgery, according to John Mackey, M.D., of the Cross Cancer Center in Edmonton, Alberta.

The finding comes from the international TanDEM trial, which randomized 208 patients to first-line treatment with the aromatase inhibitor Arimidex (anastrozole) or Arimidex and Herceptin (trastuzumab), Dr. Mackey told the San Antonio Breast Cancer Symposium.

Herceptin is a monoclonal antibody that binds the HER2 receptor and inhibits cellular growth. Arimidex, an aromatase inhibitor blocks the conversion of androgens to estrogen.

The main conclusion of the study, Dr. Mackey said, is that what he called "dual inhibition" can slow the return of breast cancer, although the study did not show a survival benefit for the combination.

That's in contrast to the combination of Herceptin and various forms of cytotoxic chemotherapy, which have been shown to improve survival in metastatic disease, but at the price of an increase in toxicity, Dr. Mackey said.

The median progression-free survival for women in the combination arm was 4.8 months, compared with 2.4 months for those on Arimidex alone, a difference that was statistically significant at P=0.0016. Overall survival in the combination arm was 28.5 months versus 23.9 months for Arimidex alone (P=0.33).

The study confirms that women with both pathways are "not well-served by hormonal therapy -- it's just not sufficient," Dr. Mackey said.

"The most important question, though, is should (doctors) recommend this combination approach to women," he said. "At present, I would say it is an option that should be discussed with them."

"It's an individual decision, taking into account the patient's co-morbidities, her preferences, her tolerance of the toxicity of chemotherapy," he added.

Adverse effects were not serious for the most part, although the combination arm had more events than the Arimidex arm, he said.

The study, with more than 30 months of follow-up, has the advantage of "very mature data," said Eric Winer, M.D., of the Dana-Farber Cancer Center in Boston, who moderated the session at which Dr. Mackey presented the trial.

But it addressed a relatively rare population of women and gave them a relatively small benefit, Dr. Winer said.

"While the combination led to the cancer being under control a little longer -- we're talking about a few months here -- the real question is how did the combination do versus giving anastrozole followed by trastuzumab," he said.

"While the study supports the use of both drugs together if a doctor wanted to do that, it's by no means the new standard," Dr. Winer said. "I do not believe this alters the standard of care."