Additional Relevant Details
The submission is supported by the results of the ExteNET Phase III study, in which treatment with neratinib resulted in a 33% reduction of risk of invasive disease recurrence or death versus placebo (hazard ratio = 0.67, p = 0.009). The 2-year invasive disease free survival (DFS) rate for the neratinib arm was 93.9% and the 2-year invasive DFS rate for the placebo arm was 91.6%. For the pre-defined subgroup of patients with hormone receptor positive disease, the results of the trial demonstrated that treatment with neratinib resulted in a 49% reduction of risk of invasive disease recurrence or death versus placebo (hazard ratio = 0.51, p = 0.001). For the patients with hormone receptor positive disease, the 2-year invasive DFS rate for the neratinib arm was 95.4% and the 2-year invasive DFS rate for the placebo arm was 91.2%.Results of the study were published online in The Lancet Oncology on February 10, 2016.The most frequently observed adverse event for the neratinib-treated patients was diarrhea, with approximately 39.9% of the neratinib-treated patients experiencing grade 3 or higher diarrhea (1 patient (0.1%) had grade 4 diarrhea). Patients who received neratinib in the ExteNET trial did not receive any prophylaxis with antidiarrheal agents to prevent the neratinib-related diarrhea. In patients with HER2-positive early stage breast cancer who have previously been treated with adjuvant trastuzumab and received anti-diarrheal prophylaxis with loperamide, interim results of a Phase II study of neratinib monotherapy demonstrated that treatment with prophylactic loperamide reduced the rate of grade 3 or higher diarrhea to between 13.0% and 18.5%.