Neoadjuvant pyrotinib, trastuzumab, and docetaxel for HER2-positive breast cancer (PHEDRA): a double-blind, randomized phase 3 trial

• DOI: 10.1186/s12916-022-02708-3
• Publication Date: 2022-12-27T23:02:26Z
• Authors: Jiong Wu; Zefei Jiang; Zhenzhen Liu; Benlong Yang; Hongjian Yang; Jinhai Tang; Kun Wang; Yunjiang Liu; Haibo Wang; Peifen Fu; Shuqun Zhang; Qiang Liu; Shusen Wang; Jian Huang; Chuan Wang; Shu Wang; Yongsheng Wang; Linlin Zhen; Xiaoyu Zhu; Fei Wu; Xiang Lin; Jianjun Zou
• Keywords: Tolerability; Clinical endpoint; Neoadjuvant Therapy

Pyrotinib (an irreversible pan-ErbB inhibitor) plus capecitabine has survival benefits and acceptable tolerability in patients with HER2-positive metastatic breast cancer. We further assessed addition of pyrotinib to trastuzumab docetaxel the neoadjuvant setting. In this multicenter, double-blind, phase 3 study (PHEDRA), treatment-naive women early or locally advanced cancer were randomly assigned (1:1) receive four cycles oral placebo (400 mg) once daily, intravenous (8 mg/kg loading dose, followed by 6 mg/kg) (100 mg/m2) every weeks. The primary endpoint was total pathological complete response (tpCR; ypT0/is ypN0) rate per independent central review. Between Jul 23, 2018, Jan 8, 2021, 355 assigned, 178 group 177 group. majority completed treatment as planned (92.7% 97.7% groups, respectively). tpCR 41.0% (95% CI 34.0 48.4) compared 22.0% 16.6 28.7) (difference, 19.0% [95% 9.5 28.4]; one-sided P < 0.0001). objective investigator 91.6% 86.6 94.8) 81.9% 75.6 86.9) after treatment, resulting an increase 9.7% 2.7 16.6). most common grade worse adverse events diarrhea (79 [44.4%] nine [5.1%] group), neutropenia (33 [18.5%] 36 [20.3%]), decreased white blood cell count (29 [16.3%] 24 [13.6%]). No deaths reported during treatment. met. Neoadjuvant pyrotinib, trastuzumab, significantly improved placebo, docetaxel, manageable toxicity, providing a new option for ClinicalTrials.gov, NCT03588091.