Neratinib is predominantly metaboli

Neratinib is predominantly metabolized by the CYP3A4 isoenzyme. Although the protocol recommended that strong CYP3A4 inducers or inhibitors should be avoided during the treatment period, 298 patients received drugs that were CYP3A4 inhibitors. Overall, there were no notable differences in the incidence of TEAEs reported in these patients compared with those who did not receive any CYP3A4 inhibitors. There were higher percentages of Grade 3 or 4 TEAEs, SAEs, and TEAEs leading to hospitalization or TEAEs leading to dose holds in patients who received concomitant CYP3A4 inhibitors (42.3%, 12.4%, 11.7%, and 39.3%, respectively) compared with patients who did not receive CYP3A4 inhibitors (30.1%, 6.0%, 5.3%, and 27.8%); however, the number of patients are small in the CYP3A4 inhibitor group making comparisons difficult. The respective higher incidences were reflected fairly consistently both in the neratinib arm and in the placebo arm in each case.