Pyrotinib Plus Trastuzumab and Docetaxel with Different Antidiarrheal Strategies in Patients with HER2-Positive Recurrent or Metastatic Breast Cancer (PHAENNA): A Multicenter, Phase 1 Trial.

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.