Rationale and design of a phase II trial of pyrotinib in combination with nab-paclitaxel as adjuvant therapy for N0/N1mi, HER2 + early breast cancer (PHAEDRA)

Changjun Wang, Yidong Zhou, Yan Lin, Feng Mao, Jinghong Guan, Xiaohui Zhang, Songjie Shen, Xuejing Wang, Yanna Zhang, Bo Pan, Ying Zhong, Li Peng, Xi Cao, Ru Yao, Xingtong Zhou, Chi Xu, Ying Xu, Qiang Sun, Changjun Wang, Yidong Zhou, Yan Lin, Feng Mao, Jinghong Guan, Xiaohui Zhang, Songjie Shen, Xuejing Wang, Yanna Zhang, Bo Pan, Ying Zhong, Li Peng, Xi Cao, Ru Yao, Xingtong Zhou, Chi Xu, Ying Xu, Qiang Sun

Abstract

Background: The de-escalation treatment in patients with low-risk HER2-positive early breast cancer (eBC) is an attractive strategy to avoid unnecessary treatment and improve the quality of life of patients. Pyrotinib, a novel irreversible pan-HER2 tyrosine kinase inhibitor (TKI), has shown efficacy in patients with advanced HER2-positive breast cancer. Meanwhile, nanoparticle albumin-bound (nab)-paclitaxel reveals survival benefit over solvent-based paclitaxel and eliminates the toxicities associated with the solvent. However, the efficacy and safety of pyrotinib in combination with nab-paclitaxel as adjuvant therapy for low-risk HER2 + eBC patients have not been evaluated.

Methods: This is a multicenter, open-label, single-arm phase II study. A sample size of 261 patients with tumor ≤ 3 cm, lymph node-negative (N0) or micrometastatic (N1mi), HER2 + breast cancer will be recruited. Eligible patients will receive nab-paclitaxel 260 mg/m2 once every 3 weeks for 12 weeks and pyrotinib 400 mg once daily for one year. The primary endpoint is invasive disease-free survival. A sub-study will be conducted to investigate different prophylactic strategies for diarrhea, which is the most common adverse event of pan-HER TKIs. One hundred and twenty patients from the main study will be randomly (1:1) allocated to receive loperamide either during the first cycle (4 mg tid on days 1-7, then 4 mg bid on days 8-21) or the first 2 cycles (4 mg tid on days 1-7, then 4 mg bid on days 8-42). The primary endpoint of the sub-study is the incidence of grade ≥ 3 diarrhea.

Discussion: This is the first prospective study of pyrotinib in combination with nab-paclitaxel as adjuvant therapy for patients with low-risk HER2-positive eBC. It would probably provide robust evidence for de-escalating strategy of HER2-positive eBC and appropriate management for pyrotinib-related diarrhea.

Trial registration: ClinicalTrials.gov Identifier: NCT04659499 . Registered on December 9, 2020.

Keywords: Adjuvant therapy; Breast cancer; Human epidermal growth factor receptor 2; Nab-paclitaxel; Protocol; Pyrotinib.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Study design

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