Two Drugs that Hit One Target Show Efficacy against Metastastic Breast Cancer

Combining two drugs that target the HER2 protein, trastuzumab (Herceptin) and the investigational agentpertuzumab, with chemotherapy may be a new treatment option for women with HER2-positive metastatic breast cancer, according to results from a large clinical trial.

The phase III CLEOPATRA trial showed that combining both of the HER2-targeting agents with the chemotherapy drug docetaxel as an initial treatment led to a 6-month improvement in progression-free survivalcompared to treatment with docetaxel and trastuzumab alone. The results were presented at the San Antonio Breast Cancer Symposium and published in the New England Journal of Medicine last week.

Targeting HER2 with two different drugs has shown promise in multiple trials, said the trial’s lead investigator, Dr. José Baselga of Harvard Medical School and the Massachusetts General Hospital, during a press briefing. “I think dual HER2 blockade is coming soon, and it will be in our daily practices.”

Although both drugs target the HER2 protein on the surface of cancer cells, they do so in different ways. Laboratory studies have indicated that the drugs may have a synergistic effect on HER2-positive tumors, which Dr. Baselga explained, are “addicted” to HER2 signaling.

More than 800 women were enrolled in the randomized trial; half received all three drugs and half received trastuzumab and docetaxel, a standard first-line treatment for women with metastatic HER2-positive breast cancer, plus a placebo. Progression-free survival was 18.5 months in the three-drug arm and 12.4 months in the two-drug plus placebo arm. More women who received the three-drug combination experienced significant shrinkage of their tumors than women who received trastuzumab, docetaxel, and the placebo, Dr. Baselga reported.

Although there is a trend toward better overall survival in women treated with pertuzumab, the trial hasn’t been running long enough to clearly determine whether the three-drug combination helps women live longer, Dr. Baselga said.

Trastuzumab has been associated with significant cardiac side effects in some women, but no increase in such side effects was seen in women in the trial who received both HER2-targeted drugs.

Genentech, which manufactures pertuzumab and trastuzumab and funded the trial, has submitted an application to the Food and Drug Administration for approval of pertuzumab for use as an initial treatment in women with HER2-positive metastatic breast cancer.

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