Efficacy and safety of HER2 inhibitors in combination with or without pertuzumab for HER2-positive breast cancer: a systematic review and meta-analysis.

Abstract

Background Although the dual anti-HER2 therapy, namely, pertuzumab plus trastuzumab and docetaxel, has shown promising results in HER2+ breast cancer patients, whether the dose, efficacy and safety of this treatment differs from those of other pertuzumab-based dual anti-HER2 therapies remain controversial. This systematic review evaluates the efficacy and safety of H (trastuzumab or trastuzumab emtansine ± chemotherapy) + P (pertuzumab) compared with those of H in HER2+ breast cancer patients.

Methods A comprehensive search was performed to identify eligible studies comparing the efficacy and safety of H + P versus H. The pathologic complete response (pCR), median progression-free survival (PFS) and overall survival (OS) were the primary outcomes, and safety was the secondary outcome. A subgroup analysis of pCR according to hormone receptor (HR) status was performed. All analyses were conducted using STATA 11.0.

Results Twenty-six studies (9872 patients) were identified. In the neoadjuvant setting, H + P significantly improved the pCR [odds ratio (OR) = 1.33; 95% confidence interval (CI), 1.08-1.63; p = 0.006]. In the metastatic setting, H + P significantly improved PFS [hazard ratios (HRs) = 0.75; 95% CI, 0.68-0.84; p

Conclusions Our study confirms that H + P is superior to H in the (neo)adjuvant treatment of HER2+ breast cancer, and increase the risk of acceptable and tolerable toxicity (rash, diarrhea, epistaxis, mucosal inflammation, and anemia). Trial registration A systematic review protocol was registered with PROSPERO (identification number: CRD42018110415 ).