The phase 3 PHILA trial compared pyrotinib (400 mg daily) or placebo in combination with trastuzumab and docetaxel in 590 patients with untreated HER2-positive metastatic breast cancer. After a median follow-up of 35.7 months in the pyrotinib group and 34.3 months in the placebo group, 59 (20%) patients in the pyrotinib group and 87 (30%) in the placebo group died. Overall survival was longer in the pyrotinib group with a hazard ratio of 0.64 (95% CI 0.46–0.89; P=0.004), a median not reached in either group. Progression-free survival was maintained at 22.1 months (95% CI 19.3–27.8) versus 10.5 months (95% CI 9.5–12.4), hazard ratio 0.44 (95% CI 0.36–0.53; P<0.001). Adverse events remained consistent with previous findings, with no new safety signals, and decreased in incidence after docetaxel discontinuation. By May 2025, with a median of 45.5 months, the analysis confirmed the prolonged benefit of the pyrotinib regimen. The combination of pyrotinib and trastuzumab has been shown to be an effective first-line treatment for this group of patients.