FDA Approves Pertuzumab for Breast Cancer

Drug complements trastuzumab in treating metastatic HER2-positive disease.

After a 6-month priority review, the U.S Food and Drug Administration (FDA) has approved pertuzumab (Perjeta; Genentech) for the treatment of previously untreated metastatic HER2-positive breast cancer. The FDA also approved the companion diagnostic tests HercepTest and HER2 FISH pharmDx Kit from Dako Products of Glostrup, Denmark.

The go-ahead is based on phase III data from the CLEOPATRA (Clinical Evaluation of Pertuzumab and Trastuzumab) study, which followed 808 women with untreated metastatic HER2-positive breast cancer who were given either pertuzumab, trastuzumab (Herceptin; Genentech), and docetaxel or trastuzumab and docetaxel alone. The combination with pertuzumab extended median progression-free survival to 18.5 months versus 12.4 months in the group that did not get pertuzumab.

“This is a substantial improvement in progression-free survival and certainly suggests that there will be a statistically significant improvement in overall survival,” comments Eric Winer, MD, director of the Breast Oncology Center at Dana-Farber Cancer Institute in Boston.

Winer, who is not affiliated with the study, says that adding pertuzumab complements trastuzumab by creating an extra blockade of the HER2 protein, which promotes cell growth and is found in increased amounts in HER2-positive breast cancer.

“Herceptin and pertuzumab bind to different regions of the HER2 receptor,” explains Winer. “Pertuzumab appears to increase effectiveness by inhibiting signaling between HER2 and other HER family receptors, including HER3, which may be one of the ways cancers develop resistance to Herceptin.”

Researchers also suspect the binding of pertuzumab to HER2 may signal the body's immune system to attack cancer cells.

Among related clinical studies now under way, Winer points out, the phase III MARIANNE trial seeks to determine the effectiveness of pertuzumab in combination with Genentech's T-DM1 (trastuzumab emtansine).

T-DM1, which links trastuzumab with a chemotherapy agent called DM1, is among the first of a class of drugs called antibody—drug conjugates to be deployed against cancer. “It was clear very early that T-DM1 was both effective and relatively non-toxic,” Winer says. The FDA is expected to approve T-DM1 for metastatic HER2-positive breast cancer within the year.

“Importantly, HER2-positive breast cancer is heterogeneous, so it is critical to identify the best drugs for each individual patient,” he adds.