Abstract P5-11-16: The efficacy and safety of selective cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors in hormone receptor-positive (HR+), human epidermal growth factor receptor-2 negative (HER2-) advanced breast cancer (ABC): A systematic review and meta-analysis

Abstract

Abstract Background Breakthrough progress has been made in Cyclin-Dependent kinase 4 and 6 (CDK4/6) inhibitors when combined with endocrine therapy (ET) for hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC). Surprisingly, the overall survival (OS) advantage of ribociclib was reported in the MONALEESE-7 trial. This study was conducted to further evaluate the efficacy and safety of CDK4/6 inhibitors for HR+/HER2- ABC. MethodWe searched PUBMUD, MEDLINE, EMBASE et al to identify relevant randomized controlled trials that compared CDK4/6 inhibitors plus ET to ET alone in HR+/HER2- ABC. We extracted the hazard ratios (HRs) for progression-free survival (PFS) and OS, and risk ratios (RRs) for objective response rate (ORR), clinical benefit rate (CBR), adverse events (AEs). Statistical analysis was performed with random-effects model. Heterogeneity was assessed by I2 statistic. Result Eight trials and 4,580 patients were included in this meta-analysis. Both PFS (HR=0.54, 95% confidence interval [CI]: 0.50-0.59, p<0.00001) and OS (HR=0.79, 95% CI: 0.67-0.93, p=0.004) were significantly improved with CDK4/6 inhibitors for HR+/HER2- ABC. Similarly, the benefit was also manifested in ORR (RR=1.47, 95%CI: 1.30-1.67, p<0.00001) and CBR (RR=1.20, 95%CI: 1.12-1.30, p<0.00001). The improvement of PFS were observed in the combined treatment group, as both first-line (HR=0.56) and second-line therapy (HR=0.53), and irrespective of menopausal statue, the presence of visceral metastasis, previous treatment with chemotherapy, their race or age. Nevertheless, more toxicity profiles were observed with CDK4/6 inhibitors. The most common Grade 3-4 AEs is neutropenia (RR 31.95). Conclusion Substantial advantages of PFS and OS was observed for CDK4/6 inhibitors in HR+/HER2- ABC. Furthermore, the benefit of PFS was across all subgroups. Though associated with an increasing occurrence of AEs, most of which are reversable, manageable and acceptable. Therefore, CDK4/6 inhibitors could be recommended as the preferred options for HR+/HER2- ABC. Citation Format: Li Jing, Fu Fangmeng, Yu Liuwen, Huang Meng, Lin Yuxiang, Mei Qian, Lv Jinxing, Wang Chuan. The efficacy and safety of selective cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors in hormone receptor-positive (HR+), human epidermal growth factor receptor-2 negative (HER2-) advanced breast cancer (ABC): A systematic review and meta-analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-11-16.