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

摘要

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??0.001]. There was a trend towards better OS but that it did not reach statistical significance (HRs?=?0.81; 95% CI, 0.64-1.03; p?=?0.082). A subgroup analysis revealed that the HER2+/HR- patients who received H?+?P showed the highest increase in the pCR. Rash, diarrhea, epistaxis, mucosal inflammation, and anemia were significantly more frequently observed with H?+?P than with H, whereas myalgia was less frequent (OR?=?0.91; 95% CI, 0.82-1.01; p?=?0.072), and no significant difference in cardiac toxicity was observed between these therapies (OR?=?1.26; 95% CI, 0.81-1.95; P?=?0.309).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 ).