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

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