Less Diarrhea Seen When Neratinib Given in Dose-Escalated Fashion for Breast Cancer

In Clinical Studies News by Barbara Jacoby

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By: Christina Bennett, MS

From: cancertherapyadvisor.com

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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.

Visit Cancer Therapy Advisor’s conference section for more coverage of the 17th St. Gallen International Breast Cancer Symposium.

Reference

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.