Quantitative evaluation of the efficacy and safety profiles of two types of targeted inhibitors combined with endocrine therapy in ER+/HER2- metastatic breast cancer

Purpose The aim of this study was to quantitatively compare the efficacy and safety of CDK4/6 inhibitors and PI3K/AKT/mTOR inhibitors for ER+/HER2- metastatic breast cancer. Methods A parametric survival function was used to analyze the time course of overall survival (OS) and progression-free survival (PFS). The objective response rate (ORR) and the incidence of any grade and grade 3–4 adverse events were summarized using the random-effects model of a single-arm meta-analysis. Results This study included 44 arms from 48 publications, with a total sample size of 7,881 patients. Our study revealed that CDK4/6 inhibitors had a median OS of 40.7 months, a median PFS of 14.8 months, and ORR of 40%. Whereas, PI3K/AKT/mTOR inhibitors had a median OS of 29.8 months, a median PFS of 8.3 months, and ORR of 20%. Additionally, this study also found that the proportion of patients with visceral metastases and specific endocrine therapy used in combination significantly impact OS and PFS. In terms of adverse events, CDK4/6 inhibitors exhibited a relatively high incidence of hematological adverse events. Conclusion Our study provides solid quantitative evidence for the first-line recommendation of CDK4/6 inhibitors combined with endocrine therapy for ER+/HER2- metastatic breast cancer in clinical guidelines.