The FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 12-4 recommending approval of neratinib (Nerlynx) for the extended adjuvant treatment of patients with early stage, HER2-positive breast cancer following postoperative trastuzumab (Herceptin).
The safety analysis for the primary ExteNET data review was based on 1408 patients from the neratinib arm and 1408 patients from the placebo arm. The median duration of exposure to neratinib and placebo was 11.6 months and 11.8 months, respectively.
In the neratinib arm, grade 3/4 AEs occurred in 50% of patients and led to treatment discontinuation in 28% of patients. The most common AEs leading to neratinib discontinuation were diarrhea (16.8%), vomiting (3.8%), and nausea (2.8%). In the neratinib arm, 7.3% of patients experienced non-fatal serious AEs, the most frequent being diarrhea in 22 patients versus 1 patient in the placebo arm.
Although patients in the ExteNET study were not required to receive antidiarrheal prophylaxis, the ongoing, open-label phase II CONTROL trial examined the preventative measure in HER2-positive patients who received neratinib for 1 year along with antidiarrheal prophylaxis given during the first two 28-day treatment cycles.
At the January 13, 2017, data cutoff, 137 patients had received prophylaxis with loperamide alone, 64 patients had received loperamide plus budesonide, and 10 patients had received loperamide plus colestipol. The median duration of neratinib treatment for the 3 cohorts was 9.07 months, 2.83 months, and 0.56 months, respectively.
Comparing the loperamide-alone CONTROL cohort to the safety data cohort from the ExteNET trial (n = 1408), the incidence of all-grade diarrhea was 77% versus 95%, respectively. The rates of grade 3 diarrhea were 31% versus 40%, respectively.
The rate of dose reductions (7.3% vs 26.4%) and holds (13.9% vs 33.9%) due to diarrhea were lower in the patients who received loperamide. However, the rate of discontinuation due to diarrhea was higher in the loperamide cohort at 20.4% versus 16.8% with neratinib alone.
... to read the full story