Pyrotinib Plus Trastuzumab and Docetaxel with Different Antidiarrheal Strategies in Patients with HER2-Positive
Wei Ren1, Xiuping Lai1, Guiying Bai2,3
1Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of phase I Clinical Trial Centre, Breast Tumor Centre, Medical Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Purpose:
The outcomes of different antidiarrheal strategies in HER2-positive breast cancer patients treated with pyrotinib plus trastuzumab and docetaxel are unknown.
Materials And Methods:
97 eligible patients received pyrotinib once daily from Cycle 1 Day 7 onwards, combined with intravenous trastuzumab and docetaxel on Day 1 of each 21-day cycle. In the 400PYR cohort, patients were treated with 400 mg pyrotinib, without mandatory antidiarrheal prophylaxis. In the 320PYR+Pro-L and 400PYR+Pro-L cohorts, patients were given 320 or 400 mg pyrotinib and loperamide prophylaxis. In the 320PYR cohort, patients were treated with 320 mg pyrotinib, without mandatory antidiarrheal prophylaxis. In the PYR-DE+Pro-L cohort, patients were treated with escalating pyrotinib doses and loperamide prophylaxis.
Results:
The incidence of grade 3 diarrhea in cohorts with loperamide prophylaxis was lower than in the 400PYR cohort. In the 3 cohorts with loperamide prophylaxis, the dose escalation cohort had the lowest incidence of grade 3 diarrhea. The incidence of grade 3 diarrhea in 320PYR cohort was similar to the 3 cohorts with prophylactic antidiarrheal loperamide. No event of grade 4 or 5 diarrhea was reported.
Conclusion:
Loperamide prophylaxis and pyrotinib dose escalation were associated with lower observed rates of grade 3 diarrhea in patients receiving pyrotinib plus trastuzumab and docetaxel. The lower rate observed in the 320PYR cohort should be interpreted cautiously and may reflect improved clinical management rather than a reproducible protocolized intervention.
