Originally published by 2 Minute Medicine® (view original article). Reused on AccessMedicine with permission.

1. This phase 3 randomised trial demonstrated that compared with placebo in combination with trastuzumab and docetaxal, pyrotinib in the same combination conferred significantly improved progression-free survival in patients with human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer.

Evidence Rating Level:1 (Excellent)

HER-2 breast cancer makes up approximately 20% of all breast cancers. Pyrotinib is a small molecule, irreversible, pan-HER receptor tyrosine kinase inhibitor that targets epidermal growth factor receptor and HER2, as well as HER4. This randomized, double-blind, multicentre, phase 3 trial involving 590 patients with HER2-positive metastatic breast cancer, aims to evaluate the efficacy of pyrotinib compared with placebo, both in combination with trastuzumab and docetaxel. Patients were randomly assigned in a 1:1 ratio to the pyrotinib group (median age [IQR] 52 [46-58] years) and placebo group (median age [IQR] 52 [46-57] years), comprising 297 and 293 patients, respectively. Pyrotinib, trastuzumab, and docetaxel, significantly improved progression-free survival compared with the placebo in the same combination (24.3 [95% CI 19.1 to 33.0] months versus 10.4 [9.3 to 12.3] months; hazard ratio 0.41 [0.32 to 0.53]; one sided P<0.001). These findings were consistent in subgroup analysis, including in those with and without previous (neo)adjuvant trastuzumab and varying treatment-free intervals. Objective responses were significantly higher in the pyrotinib group, with 83% (95% CI, 78% to 87%) achieving a response compared to 71% (65% to 76%) in the placebo group (difference 12.2%, [5.4% to 18.9%]; one-sided P<0.001). Patients receiving pyrotinib experienced higher rates of grade 3 or above treatment-related adverse events (90% vs. 76% in the placebo group), but no treatment-related deaths occurred. Overall, these findings demonstrate a statistically significant improvement in progression-free survival with pyrotinib in combination with trastuzumab and docetaxel compared with placebo, with a manageable safety profile. This treatment regimen could constitute a novel first-line therapy for patients with HER2-positive metastatic breast cancer.

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