Different treatment durations of loperamide in preventing pyrotinib-induced diarrhea: A randomized, parallel-group sub-study of the phase II PHAEDRA trial

BackgroundPyrotinib, a pan-HER tyrosine kinase inhibitor, demonstrates efficacy in the treatment of HER2-positive breast cancer. However, the frequent occurrence of treatment-emergent diarrhea necessitating discontinuation, impacts patient outcomes. MethodsIn this multicenter, open-label, phase II PHAEDRA study enrolling early stage HER2-positive patients for postoperative treatment with nab-paclitaxel and pyrotinib, 120 patients were included in a sub-study and randomly divided into two groups to receive 21 days and 42 days of loperamide for primary prophylaxis of diarrhea, followed by as-needed usage. The primary outcome was the incidence of grade [≥]3 diarrhea. ResultsFifty-eight patients in the 21-day group and 59 patients in the 42-day group received at least one dose of pyrotinib. With a median follow-up of 12.1 months, all patients experienced diarrhea of any grade, with grade [≥]3 events in 39.7% of the 21-day group and 42.4% of the 42-day group (relative risk: 0.94; 95% confidence interval: 0.61-1.45). The most common treatment-emergent adverse events, other than diarrhea, were hypoesthesia, vomiting, nausea, and rash, mostly grade 1-2, except for one patient with a grade [≥]3 decreased neutrophil count in each group. ConclusionNo significant differences were observed between 21-day and 42-day loperamide durations in preventing grade [≥]3 diarrhea. Considering the economic cost and patient compliance, 21-day loperamide prophylaxis might represent a more pragmatic and appropriate approach for clinical application. Trial registration: ClinicalTrials.gov, NCT04659499