Meta-analysis of Clinical Efficacy and Safety of Pertuzumab and Trastuzumab Combined Therapy in HER-2 Positive Breast Cancer

Objective: To systematically evaluate the clinical efficacy and safety of pertuzumab and trastuzumab combined therapy in human epidermal growth factor receptor 2 (HER-2) positive breast cancer through a meta-analysis. Methods: English databases including PubMed, Embase, and the Cochrane Central Register of Controlled Trials, as well as Chinese databases including China National Knowledge Infrastructure, Wanfang Database, and the Chinese Biomedical Literature Service System (Sinomed), were searched for randomized controlled trials (RCTs) comparing pertuzumab and trastuzumab combined therapy (experimental group) with trastuzumab alone (control group) for the treatment of HER-2 positive breast cancer. The literature search time was from the establishment of the database to July 2022. Two reviewers independently screened the literature, extracted data, and assessed the quality of the literature. Meta-analysis was performed using Review Manager 5.4 software. Results: A total of 9 RCTs involving 7199 patients were included in the meta-analysis. The results of the effectiveness indicators showed that the risk of tumor progression in HER-2 positive breast cancer patients receiving dual-targeted therapy was significantly lower than that in patients receiving trastuzumab alone [Hazard ratios (HR) = 0.68, 95% confidence intervals (CI) (0.58, 0.79), P<0.00001]; the overall survival (OS) of HER-2 positive breast cancer patients receiving dual-targeted therapy was significantly longer than that of patients receiving trastuzumab alone [HR=0.73, 95% CI (0.59, 0.88), P<0.0009]. In terms of safety, there was no statistical difference in the incidence of severe adverse events and ≥3 grade neutropenia between the experimental and control groups (P>0.05), but the incidence of ≥3 grade diarrhea in the experimental group was significantly higher than that in the control group [relative risks = 2.44, 95% CI (1.95, 2.99), P<0.00001]. Conclusion: The combined therapy of pertuzumab and trastuzumab has significant clinical efficacy in HER-2 positive breast cancer patients, and its application can further improve patients' progression-free survival and OS. However, it also increases the risk of adverse reactions to a certain extent. Therefore, in clinical practice, it is necessary to strengthen the monitoring and protection of relevant adverse reactions in patients.