The FDA approved pertuzumab to treat patients with HER-2–positive metastatic breast cancer who have not received prior anti-HER-2 treatment or chemotherapy.
Pertuzumab (Perjeta, Genentech), a humanized monoclonal antibody that is administered intravenously, is given in combination with the anti–HER-2 therapy trastuzumab (Herceptin, Genentech) and docetaxel, a form of chemotherapy.
“Since trastuzumab was first approved more than a decade ago, continued research has allowed us to better understand the role HER-2 plays in breast cancer,” Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in an FDA press release. “This research provided the background to combine two targeted drugs — trastuzumab and [pertuzumab] — with docetaxel to slow disease progression in breast cancer.”
Production issues may potentially affect the long-term supply of pertuzumab, according to the FDA.
“Given the need for additional treatments for metastatic breast cancer, we made the decision to approve this drug … and not to delay its availability to patients pending resolution of the production issues relating to future supply,” Janet Woodcock, MD, director of FDA’s Center for Drug Evaluation and Research, said in the press release. “Genentech is currently developing a plan to mitigate the effect on patients of any potential shortage.”
The FDA based its approval — granted under the agency’s priority review program — on results of the international CLEOPATRA trial. The randomized, double-blind, placebo-controlled phase 3 trial involved 808 patients with previously untreated HER-2–positive metastatic breast cancer, or patients with HER-2–positive metastatic breast cancer that had recurred after therapy in the adjuvant or neoadjuvant setting.
Researchers randomly assigned the patients to receive pertuzumab, trastuzumab and docetaxel, or trastuzumab, docetaxel and placebo.
The primary endpoint was PFS.
Patients who received the pertuzumab combination had a median PFS of 18.5 months vs. 12.4 months for patients whose combination included the placebo. The results suggest pertuzumab reduced risk of disease progression or death by 38% (HR=0.62; P<.0001).
Side effects reported by more than 30% of patients in the pertuzumab group were diarrhea, hair loss, a decrease in white blood cell count, nausea, fatigue, rash and peripheral sensory neuropathy. Grade-3/grade-4 adverse events reported by more than 2% of patients were low white blood cell count, low white blood cell count with fever, diarrhea, peripheral neuropathy, a decrease in red blood cell count, weakness and fatigue.