Pyrotinib or placebo in combination with trastuzumab and docetaxel for HER2 positive metastatic breast cancer: long term survival results from randomised phase 3 PHILA trial
Year: 2026
Type: article
Study design: Clinical Trial
Abstract: Objective To report updated results of the phase 3 PHILA trial, which evaluated the efficacy and safety of pyrotinib or placebo in combination with trastuzumab and docetaxel in patients with untreated human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer. Design Multicentre, double blind, randomised, placebo controlled phase 3 trial. Setting 40 centres in China, 6 May 2019 to 17 January 2022. Participants 590 female patients with untreated HER2 positive metastatic breast cancer. Interventions Eligible patients were randomly assigned in a 1:1 ratio to receive either the irreversible pan-HER inhibitor pyrotinib (400 mg orally once daily) or placebo, both in combination with intravenous trastuzumab (8 mg/kg for the first cycle, then 6 mg/kg in subsequent cycles) and docetaxel (75 mg/m 2 ) on day 1 of each 21 day treatment cycle. Main outcome measure The primary endpoint was investigator assessed progression-free survival. Results 590 patients were randomised and received treatment (297 in the pyrotinib group and 293 in the placebo group). As of 30 April 2024, during a median follow-up of 35.7 months in the pyrotinib group and 34.3 months in the placebo group, 59 (20%) and 87 (30%) patients died, respectively. Overall survival was longer in the pyrotinib group (hazard ratio 0.64 (95% confidence interval (CI) 0.46 to 0.89); nominal one-sided P=0.004). At end of follow-up, neither group had reached the median overall survival. Improvement in progression-free survival in the pyrotinib group was maintained (22.1 months (95% CI 19.3 to 27.8) v 10.5 months (9.5 to 12.4), hazard ratio 0.44 (95% CI 0.36 to 0.53); nominal one sided P<0.001). Adverse event profiles remained consistent with the interim analysis for type, frequency, and severity. After discontinuation of docetaxel, the overall incidence of adverse events decreased substantially. As of 30 May 2025, with a median follow-up of 45.5 months, the pyrotinib based regimen showed consistent and prolonged survival benefit. Conclusions The updated analysis of the phase 3 PHILA trial confirmed the superiority of pyrotinib in combination with trastuzumab and docetaxel over placebo in combination with trastuzumab and docetaxel in sustaining longer progression-free survival and improving overall survival for initial treatment of HER2 positive metastatic breast cancer. The safety profile remained consistent with interim findings, with no new safety signals identified during extended follow-up. This analysis reinforces the efficacy of this dual anti-HER2 (pyrotinib plus trastuzumab) regimen as an effective treatment strategy for this patient population. Trial registration ClinicalTrials.gov NCT03863223 .
Source: BMJ
Authors: Fei Ma, Min Yan, Wei Li, Quchang Ouyang, Zhongsheng Tong, Yuee Teng, Yongsheng Wang, Shusen Wang, Cuizhi Geng, Ting Luo, Jincai Zhong, Qingyuan Zhang, Qiang Liu, Xiaohua Zeng, Tao Sun, Qinguo Mo, Shoubing Zhou, Peidong Li, Jing Cheng, Xiaojia Wang, Jianyun Nie, Jin Yang, Xinhong Wu, Xinshuai Wang, Huiping Li, Guangyu Yao, Yang Fan, Jiaman Lin, Xiaoyu Zhu, Binghe Xu
Institutions: Chinese Academy of Medical Sciences & Peking Union Medical College, Cancer Hospital of Chinese Academy of Medical Sciences, Zhengzhou University, Henan Cancer Hospital, First Hospital of Jilin University, Central South University, Hunan Cancer Hospital, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, First Hospital of China Medical University, Shandong Tumor Hospital, Sun Yat-sen University Cancer Center, Hebei Medical University, Fourth Hospital of Hebei Medical University, Sichuan University, West China Hospital of Sichuan University, First Affiliated Hospital of GuangXi Medical University, Third Affiliated Hospital of Harbin Medical University, Sun Yat-sen University, Sun Yat-sen Memorial Hospital, Chongqing University, Liaoning Cancer Hospital & Institute, China Medical University, Guangxi Medical University, Tumor Hospital of Guangxi Medical University, University of Science and Technology of China, Jilin Province Tumor Hospital, Wuhan Union Hospital, Huazhong University of Science and Technology, Henan University of Science and Technology, Zhejiang Cancer Hospital, First Affiliated Hospital of Henan University of Science and Technology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, Hubei Cancer Hospital, Peking University Cancer Hospital, Nanfang Hospital, Southern Medical University, Jiangsu Hengrui Medicine (China)
Language: English
Topic: HER2/EGFR in Cancer Research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W7137156744