The FDA’s Oncologic Drugs Advisory Committee (ODAC) has voted 12 to 4 in favor of approving the experimental breast cancer drug neratinib (Nerlynx, Puma Biotechnology) for use in patients who have already had their tumors surgically removed. The panel observed, however, that the treatment’s clinical benefit was only “modest.”
The committee’s opinions are not binding but are considered by the FDA in its decision-making process.
In July 2016, Puma submitted a new drug application in support of the use of neratinib as a single agent for the extended adjuvant treatment of adults with early-stage receptor tyrosine-protein kinase ERBB2-positive breast cancer who have received adjuvant trastuzumab-based therapy.
Neratinib is a kinase inhibitor that irreversibly binds to epidermal growth factor receptors (EGFRs), to human epidermal growth factor receptor 2 (HER2), and to HER4.
Puma conducted a multicenter, randomized, double-blind, placebo-controlled study of neratinib versus placebo in women with early-stage HER2-overexpressed/amplified breast cancer after adjuvant treatment with trastuzumab. According to the FDA panel, the trial underwent several major unplanned amendments that affected enrollment, the number of invasive disease-free survival (iDFS) events observed, and the period of patient follow-up.
The primary analysis showed an improvement with neratinib, with an absolute difference in iDFS of 2.8% compared with placebo after a two-year follow-up (P = 0.008).
The tolerability of neratinib in this patient population caused some concern to committee members, however, given the frequent dose interruptions, reductions, and discontinuations that were observed, mostly due to diarrhea. In the pivotal study, nearly all patients experienced diarrhea (any grade), and 40% of the patients experienced grade-3 diarrhea.