Crofelemer for the Management of Neratinib-Associated Diarrhea in Patients With HER2+ Early-Stage Breast Cancer.

Background: To evaluate the efficacy of crofelemer, a first in class anti-secretory anti-diarrheal agent, to manage neratinib-induced diarrhea in patients with early-stage breast cancer taking adjuvant neratinib.

Patients And Methods: This single center, open label trial enrolled patients with Stage 2 to 3 HER2+ breast cancer taking adjuvant neratinib. One cohort took prophylactic crofelemer 125 mg bid and loperamide in the first 2 cycles, and as needed in subsequent cycles. The second cohort took dose-escalated neratinib with loperamide as needed (DE cohort). The primary endpoint was incidence of grade ≥ 3 diarrhea in the first 2 cycles.

Results: Seven patients in the crofelemer cohort and 4 in the DE cohort were enrolled. In the first 2 cycles, 2 patients (29%) in the crofelemer cohort and 2 patients (50%) in the DE cohort experienced grade 3 diarrhea lasting 1 day on average. After cycle 2, no additional patients in either cohort had grade 3 diarrhea. Five of 7 patients controlled diarrhea with crofelemer alone. There were no grade 4 diarrhea events in either cohort. Three patients in the crofelemer cohort dose-reduced neratinib due to diarrhea in the first 2 cycles. Patients in the crofelemer cohort had an average of 0.58 diarrhea episodes/day. 82% experienced constipation, all grade 1.

Conclusions: This is the first study to investigate crofelemer for neratinib-induced diarrhea and demonstrates crofelemer activity in this setting. Further investigation of crofelemer for diarrhea secondary to cancer treatment is needed.