Efficacy and Safety of Trastuzumab Combined with Pertuzumab for Human Epidermal Growth Factor Receptor-2-Positive Breast Cancer: A Meta-Analysis Study of Randomized Control Trials

Abstract

Objective. This systematic review was aimed to evaluate the efficacy and safety of trastuzumab in combination with pertuzumab for human epidermal growth factor receptor-2 (HER2)-positive breast cancer (BC). Methods. A comprehensive search of PubMed, Web of Science, Embase, China National Knowledge Internet, and Wanfang databases was conducted. All randomized controlled trials on trastuzumab in combination with pertuzumab for HER2-positive BC from the time of database construction to October 2022 were included. A meta-analysis of the included literature was performed using STATA 17.0 software. Results. A total of 8 studies were included, involving a total of 7628 patients, including 3814 patients in the treatment group and 3814 patients in the control groups. The results of the meta-analysis showed that the median progression-free survival was much shorter in the treatment group (trastuzumab combined with pertuzumab) than in the control group (placebo) (OR = 0.656, 95% CI (0.581, 0.741), $P$  < 0.001) and that patients in the treatment group experienced significantly more cases of diarrhea than those in the control group (OR = 2.429, 95% CI (2.065, 2.856), $P$  < 0.001) while experiencing significantly less cases of constipation (OR = 0.641, 95% CI (0.473, 0.869), $P$  = 0.004). Notably, the incidence of nausea and vomiting did not differ significantly between the two groups. In addition, there was no significant difference between the two groups in the incidence of systemic adverse effects such as neutropenia, fatigue, myalgia, and cardiac disease ( $P$  > 0.05). However, the treatment group had a much higher incidence of rash than the control group (OR = 1.915, 95% CI (1.505, 2.437), $P$  < 0.001). The risk of serious adverse reactions was markedly higher in patients in the treatment group than that in the control group (OR = 1.342, 95% CI (1.206, 1.494), $P$  < 0.001). Conclusion. The combination of trastuzumab and pertuzumab was not effective in improving the intermediate progression-free survival of patients. However, adverse effects, including diarrhea and rash, are the limiting factors for the current promotion of this combination method.