Two Drugs that Hit One Target Show Efficacy against Metastatic Breast Cancer
Combining two drugs that target the HER2 protein, trastuzumab (Herceptin®) and pertuzumab (Perjeta™), with chemotherapy is a new treatment option for women with HER2-positive metastatic breast cancer, according to results from a large clinical trial.
The initial results of 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 survival compared with treatment with docetaxel and trastuzumab alone. The results were presented on December 7, 2011, at the San Antonio Breast Cancer Symposium (SABCS) and published the same day in the New England Journal of Medicine.
Targeting HER2 with two different drugs has shown promise in multiple trials, said the trial’s lead investigator, José Baselga, MD, PhD, of Harvard Medical School and the Massachusetts General Hospital, during an SABCS 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. Median 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 substantial shrinkage of their tumors than women who received trastuzumab, docetaxel, and the placebo.
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.
The initial analysis showed a trend toward better overall survival in women treated with pertuzumab, trastuzumab, and docetaxel than in women treated with placebo, trastuzumab, and docetaxel, but the study had not gone on long enough for the survival data to be definitive.
On April 18, 2013, the study investigators reported an interim analysis of overall survival after an additional year of follow-up. They found that women treated with pertuzumab, tratsuzumab, and docetaxel lived longer than those in the two drug plus placebo group. At 30 months of follow-up, more than half of the women treated with pertuzumab were still alive, while the median overall survival for women in the placebo-containing group was 37.6 months. The risk of death at the time of the analysis was 34 percent lower for women in the pertuzumab group than for women in the placebo group. The findings were published in The Lancet Oncology.
The Food and Drug Administration approved pertuzumab on June 8, 2012, for use in combination with trastuzumab and docetaxel to treat women with HER2-positive metastatic breast cancer. This approval was based on the earlier progression-free survival results.