If the independent Oncologic Drug Advisory Committee recommends approval, the FDA itself will begin reviewing the therapy.
The regulator accepted Puma’s New Drug Application for neratinib in September 2016. The application asked the FDA to approve the drug for early-stage HER2-positive breast cancer patients who were treated previously with a regimen that included Herceptin (trastuzumab).
Puma submitted the application after findings in the Phase 3 ExteNET trial (NCT00878709) and the Phase 2 CONTROL trial (NCT02400476) proved promising. The trials tested neratinib as an extended adjuvant — or post-surgery — treatment for patients with early-stage, HER2-positive breast cancer.
ExteNET was a double-blind, placebo-controlled trial designed to assess the safety and effectiveness of neratinib versus a placebo after adjuvant Herceptin therapy. It covered 2,840 patients in 41 countries who had surgery followed by Herceptin. Patients were randomized to receive either neratinib or a placebo for a year.
After the treatment, researchers followed patients for two years to see whether they were still alive, their cancer had recurred, or they had developed a form of breast cancer called ductal carcinoma in situ that can become aggressive later. The primary goal of the study was to see if neratinib led to disease-free survival.
Neratinib reduced by 33 percent the number of patients who died or had their cancer recur, compared with placebo, researchers said. The results were particularly striking in a subgroup of patients with hormone receptor-positive breast cancer. Neratinib reduced by 49 percent the number of those patients who died or had a recurrence.
The most common adverse event in neratinib-treated patients was diarrhea, with nearly 40 percent experiencing a severe form. Chemotherapy often leads to diarrhea.
Puma decided to conduct a Phase 2 CONTROL trial to investigate the effectiveness of loperamide prophylaxis, with or without other agents, in reducing neratinib-related diarrhea.
Data presented at the American Association for Cancer Research annual meeting in Washington revealed that 11.5 percent to 30.7 percent of breast cancer patients experience severe diarrhea. The percentage depended on which treatment they took.
Importantly, while patients in the ExteNET trial reported persistent diarrhea during the treatment period, patients in the CONTROL trial reported early but not recurring diarrhea.