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Administering neratinib in a dose-escalated fashion with optional loperamide was found to reduce the incidence of severe diarrhea in patients with HER2-positive, early-stage breast cancer, according to data from the phase 2 CONTROL trial reported at the 17th St. Gallen International Breast Cancer Conference 2021.
The CONTROL trial (ClinicalTrials.gov Identifier: NCT02400476) enrolled 563 patients with stage I to IIIC HER2-positive breast cancer who completed trastuzumab-based adjuvant therapy. The study included 6 cohorts: 4 cohorts in which patients were treated with various loperamide-based antidiarrheal strategies and 2 dose-escalation cohorts.
Patients in dose-escalation cohort 1 (60 patients) received neratinib 120 mg/d for the first week. The dose was escalated to 160 mg/d during the second week and then to 240 mg/d during the third week and continued at that dosage for up to 1 year. Loperamide was administered as needed.
Patients in dose-escalation cohort 2 (62 patients) received neratinib 160 mg/d for the first 2 weeks. The dose was escalated to 200 mg/d for the third and fourth weeks and then to 240 mg/d for the fifth week and continued at that dosage for up to 1 year. Loperamide was administered as needed.
Compared with the ExteNET adjuvant trial, for which the incidence of grade 3 diarrhea was 40% with neratinib, and the other cohorts in the CONTROL trial, the lowest rate of grade 3 diarrhea (13.3%) was seen in dose-escalation cohort 1. For dose-escalation cohort 2, the incidence of grade 3 diarrhea was 25.8%.
No grade 4 diarrhea was seen in either dose-escalation cohort, and discontinuation rates due to diarrhea were low (3.3% for dose-escalation cohort 1 and 4.8% for dose-escalation cohort 2).
The median cumulative duration of grade 3 diarrhea was 2.5 days (range, 1-6 days) for patients in the dose-escalation cohort 1 and 2 days (range, 1–7 days) for patients in dose-escalation cohort 2.
The study authors concluded that these results show improved tolerability of neratinib administered in a dose-escalated manner and suggest that the regimen used in dose-escalation cohort 1 combined with loperamide as needed allows patients to stay on neratinib longer, providing them the opportunity to receive the “full benefit” of neratinib.
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Ruiz-Borrego M, Chan A, Marx G, et al. Bringing diarrhea under CONTROL: dose escalation reduces neratinib-associated diarrhea and improves tolerability in HER2-positive early-stage breast cancer. Presented at: The 17th St. Gallen International Breast Cancer Conference 2021; March 17-21, 2021. Abstract P004.