73P Effect of diarrheal prophylaxis or dose escalation on neratinib-associated diarrhea and tolerability in patients with HER2+ early-stage breast cancer: Final findings from the CONTROL trial

Abstract

Background: Neratinib (N), an irreversible pan-HER TKI, is approved in the EU for extended adjuvant treatment of early-stage HR+ HER2+ breast cancer (BC) after adjuvant trastuzumab (T)-based therapy. The CONTROL trial (NCT02400476) investigated pre-emptive antidiarrheal prophylaxis or dose escalation (DE) for prevention of diarrhea, the most frequent side effect of N. Methods: CONTROL is an international, multi-cohort, open-label, phase 2 study. Patients (pts) 18y with stage IeIIIc HER2+ BC received oral N (240 mg/d for 1y) after T-based adjuvant therapy. Pts were enrolled sequentially into separate cohorts: 1) mandatory loperamide prophylaxis; 2) budesonide + loperamide; 3) colestipol + loperamide; 4) colestipol + loperamide PRN; 5) DE + loperamide PRN (2 cohorts). DE1 schedule: N 120 mg/d x w1, 160 mg/d x w2, then 240 mg/d from w3 to 12m. DE2 schedule: N 160 mg/d x w1&2, 200 mg/d x w3&4, then 240 mg/d from w5 to 12m. Primary endpoint: incidence of grade 3 diarrhea. Results: 563 pts were enrolled. All preventive strategies reduced grade 3 diarrhea vs ExteNET (historical control: 39%). Median cumulative duration of grade 3 diarrhea ranged from 2e3.5d in CONTROL (vs 5.0d for ExteNET). The proportion of pts discontinuing N because of diarrhea was decreased in CONTROL vs ExteNET. Key diarrhea outcomes in all CONTROL cohorts are presented in the table and will be fully detailed during the congress. Conclusions: These final findings from CONTROL show improved tolerability of N with all diarrhea prophylaxis strategies and suggest that DE1 with loperamide PRN allows pts to stay on treatm.ent longer and receive full benefit from N. Background: Better understanding of patient (pt) perspectives could help in the management of HR+, HER2-early breast cancer (EBC).