Management of Diarrhea in Patients with HER2-Positive Breast Cancer Treated with Neratinib: A Case Series and Summary of the Literature

Abstract

Introduction: Neratinib and neratinib-based combinations have demonstrated efficacy for treatment of human epidermal growth factor receptor 2-positive (HER2+) early-stage and metastatic breast cancers. However, diarrhea has been reported as a common adverse event leading to neratinib discontinuation. Results from the CONTROL trial suggest that proactive diarrhea management with antidiarrheal prophylaxis or dose escalation of neratinib from a lower starting dose to the full FDA-approved dose of 240 mg/day can reduce the incidence, duration, and severity of neratinib-associated diarrhea in patients with early-stage breast cancer. Dose escalation has been included in the FDA-approved label for both early-stage and metastatic HER2+ breast cancer since June 2021.

Case series: This series of five cases details real-world clinical implementation of strategies for management of neratinib-induced diarrhea in patients with early-stage and metastatic HER2+ breast cancer, including a patient with a pre-existing gastrointestinal disorder.

Management and outcome: In four of five cases, diarrhea was managed with neratinib dose escalation, and antidiarrheal prophylaxis with loperamide plus colestipol was used in the remaining case. Management of diarrhea allowed all patients to remain on therapy.

Discussion: This case series shows that neratinib-associated diarrhea can be managed effectively with neratinib dose escalation from a lower initial starting dose and/or prophylactic antidiarrheal medications in a real-world clinical setting. The findings highlight the importance of patient-provider communication in proactive management of adverse events. Widespread implementation of the strategies described here may improve adherence and thereby clinical outcomes for patients with HER2+ breast cancer treated with neratinib.

Keywords: Diarrhea; Early-stage breast cancer; HER2; Metastatic breast cancer; Neratinib.

Fig. 1

Neratinib initiation strategies described in this case series. DE strategies evaluated in CONTROL are shown for comparison [38]. ^aPatient was unable to escalate to 240 mg/day because of grade 2 to 3 diarrhea and instead maintained a 3-day repeating dose pattern. ^bIn combination with capecitabine (1000 mg bid). Patient reinitiated neratinib with DE after poor tolerability with a starting dose of 240 mg/day and prophylactic loperamide. bid, twice daily; DE, dose escalation; PRN, as needed; qd, daily; qw, every week; q2w, every two weeks; tid, three times daily