Abstract P1-12-03: Antidiarrheal prophylaxis with loperamide for patients with lymph node-negative (N0) or micrometastatic (N1mi), HER2-positive breast cancer who received adjuvant pyrotinib plus nab-paclitaxel: a randomized sub-study of PHAEDRA
Authors: Wang Changjun , Lin Yan , Zhou Yidong , Mao Feng , Guan Jinghong , Shen Songjie , Wang Xuejing , Zhang Xiaohui , Zhang Yanna , Pan Bo , Zhong Ying , Peng Li , Li Yan , Huang Xin , Xu Ying , Sun Qiang 
Published: March 2023

Abstract
Background: Diarrhea is the most common adverse event of pan-HER tyrosine kinase inhibitors. There is no consensus on therapeutic or prophylactic strategy of pyrotinib-related diarrhea. PHAEDRA is an ongoing multicenter, single-arm, phase II trial conducted to evaluate adjuvant pyrotinib plus nab-paclitaxel for patients with low-risk HER2-positive breast cancer. Here, we reported the results from the sub-study of PHAEDRA, which investigated the effect of different prophylactic strategies with loperamide for diarrhea. Methods: In PHAEDRA, patients with N0/N1mi, HER2-positive invasive breast cancer and primary tumor ≤3 cm received nab-paclitaxel 260 mg/m2 once every 3 weeks for 12 weeks and pyrotinib 400 mg once daily for one year within 90 days after surgery. In the sub-study, patients were randomly assigned to receive loperamide 4 mg three times a day on days 1-7 and twice a day on days 8-21 (cohort A) or days 8-42 (cohort B) since the initiation of adjuvant therapy. The primary endpoint of the sub-study was the incidence of grade ≥3 diarrhea. Results: Between January 2021 and May 2022, the enrollment of 120 patients in the sub-study was completed. Grade ≥3 diarrhea was reported in 18 (30%) of 60 patients in cohort A and 19 (32%) of 60 patients in cohort B. The median time to first grade ≥3 diarrhea was 4.5 days (IQR, 1.0-6.5) in cohort A and 4 days (IQR, 1.0-6.0) in cohort B. The median number of grade ≥3 diarrhea episodes was 1 (IQR, 1-1) in both cohorts. Three (5%) patients in each cohort had constipation events, respectively, which were all grade 1 or 2. One (2%) patient in cohort A and two (3%) in cohort B had dose reductions of loperamide due to constipation, and no patients discontinued loperamide. One (2%) patient in cohort A had dose reduction of pyrotinib and one (2%) in each cohort discontinued pyrotinib due to diarrhea. Conclusions: The effects of both loperamide regimens on antidiarrheal prophylaxis were consistent with that of loperamide prophylaxis in the CONTROL trial, but with extremely fewer constipation events. Long-course and short-course loperamide prophylaxis showed numerically similar incidence of grade ≥3 diarrhea. Proactive diarrhea management can promote the full-dose and full-course treatment with pyrotinib. It is still necessary to develop more effective antidiarrheal prophylaxis regimens for pan-HER tyrosine kinase inhibitors.
Citation Format: Changjun Wang, Yan Lin, Yidong Zhou, Feng Mao, Jinghong Guan, Songjie Shen, Xuejing Wang, Xiaohui Zhang, Yanna Zhang, Bo Pan, Ying Zhong, Li Peng, Yan Li, Xin Huang, Ying Xu, Qiang Sun. Antidiarrheal prophylaxis with loperamide for patients with lymph node-negative (N0) or micrometastatic (N1mi), HER2-positive breast cancer who received adjuvant pyrotinib plus nab-paclitaxel: a randomized sub-study of PHAEDRA [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-12-03.