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 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.