Objective To compare the efficacy and safety of pyrotinib single- and dual-targeted therapy in HER2-positive stage Ⅳ breast cancer.

Methods Clinical data from HER2-positive stage Ⅳ breast cancer patients treated with pyrotinib at the Guangxi Medical University Cancer Hospital between October 2018 and January 2025 were retrospectively collected. Based on the treatment regimen, patients were divided into the single-target group (pyrotinib alone as the targeted drug) and the double-targeted group (pyrotinib-based dual-targeted therapy). The efficacy and safety between the groups were compared, and the effects of different factors on efficacy were analyzed. Median progression-free survival (mPFS) was calculated using the Kaplan-Meier method, and prognostic factors were analyzed using Cox regression analysis.

Results A total of 59 patients were enrolled, including 27 in the single-target group and 32 in the dual-target group. The mPFS of patients in the double-target group was longer than that of the single-target group (17.1 months vs. 10.0 months), but the difference was not statistically significant (P=0.214). Multivariate Cox regression analysis showed that Eastern Cooperative Oncology Group (ECOG) score of 2 was an independent risk factor for mPFS [HR=2.892, 95%CI (1.135, 7.366), P=0.026], while no prior treatment with lapatinib was an independent protective factor for mPFS [HR=0.138, 95%CI (0.036, 0.535), P=0.004]. In terms of safety, there was no statistically significant difference in the incidence of various adverse reactions between the two groups (P > 0.05).

Conclusion Compared with the pyrotinib single-targeted therapy regimen, the pyrotinib dual-targeted therapy regimen has a longer mPFS in the treatment of HER2-positive stage Ⅳ breast cancer patients, but the difference is not statistically significant. This conclusion needs further verification through large-sample studies. ECOG score ≤1 and no prior treatment with lapatinib were independent predictors of favorable prognosis.

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