The clinical benefit of epidermal growth factor receptor and human epidermal growth factor receptor 2 targeted agents adding to endocrine therapy in hormone receptor-positive breast cancer.

OBJECTIVES:Studies have suggested that the crosstalk between estrogen receptor and ErbB receptor is involved in endocrine therapy (ET) resistance, which might be overcome by drugs-targeting ErbB receptor. However, the results of clinical studies remain controversial. The aim of this meta-analysis was to evaluate the efficacy and safety of ErbB (mainly epidermal growth factor receptor and human epidermal growth factor receptor 2 [HER2]) inhibitors added to ET for hormone receptor-positive breast cancer patients. MATERIALS AND METHODS:Eligible randomized clinical trials on ET with or without ErbB receptor-targeting inhibitors (ERTI) for hormone receptor-positive breast cancer were identified by searching the main electronic databases (up to July 2015). Revman 5.3 was used to analyze the outcomes extracted from the included trials. RESULTS:In the overall population, ERTI failed to show any significant differences on overall response rate (ORR), clinical benefit rate (CBR), and overall survival (OS). However, improvement on progression-free survival (PFS) (hazard ratio [HR] 0.84, 95% confidence interval [CI] = 0.76-0.93, P = 0.0005) was observed. For the HER2+ subgroup, ERTI could significantly improve ORR, CBR, PFS, OS, and time to progression compared to endocrine monotherapy. This improvement cannot be found in the HER2- subgroup. The risk of serious adverse events (SAEs) increased significantly when ERTI was present (RR = 2.09, 95% CI = 1.44-3.02, P < 0.0001). CONCLUSIONS:For HR+/HER2+ breast cancer, ERTI added to ET can significantly improve the clinical efficacy with the cost of increasing SAE.