Cyclin-dependent kinase 4/6 inhibitor in combination with endocrine therapy versus endocrine therapy only for advanced breast cancer: a systematic review and meta-analysis

BACKGROUND: The resistance to endocrine therapy poses a significant challenge to the management of advanced breast cancer with hormone receptor (HR) positive and human epidermal growth factor receptor 2 (Her-2) negative. The purpose of this study was to further examine the efficacy and safety of cyclin-dependent kinase 4/6 inhibitors (CDK4/6Is) in combination with endocrine therapy as a recovery treatment for advanced breast cancer patients. METHODS: The risk of bias for each included study was assessed using the Cochrane Risk of Bias Tool. The Cochrane Q value, combined with the I(2) statistics, were selected to be tested for heterogeneity across the studies. The generic inverse variance was used to pool the hazard ratio and 95% CI of progression-free survival (PFS) and overall survival (OS), while pooled RRs and 95% CI were conducted using the Mantel-Haenszel to appraise the overall response rate (ORR), clinical benefit rate (CBR), and any adverse effects. RESULTS: Eight random clinical trials were finally identified. The analysis showed that the duration of PFS was significantly longer in the CDK4/6Is group than in the control group (hazard ratio, 0.55; 95% CI, 0.51–0.60; P<0.00001), and treatment with CDK4/6Is-endocrine therapy resulted in longer OS than treatment with endocrine therapy only (hazard ratio, 0.79; 95% CI, 0.66–0.96; P=0.001). As for any adverse events, the analysis showed a remarkable rise in bone marrow suppression, especially neutropenia and leukopenia (respectively, RR =32.04; 95% CI, 17.14–59.90, RR =30.65; 95% CI, 16.51–56.91), but not in gastrointestinal toxicity. CONCLUSIONS: Highly selective CDK4/6Is were well tolerated, effective drugs in advanced breast cancer patients with HR-positive and Her-2 negative.