Efficacy and toxicity of CDK 4/6 inhibitors in breast cancer: Systematic review and meta-analysis of the phase III clinical trials.

Abstract

e14591 Background: Selective CDK4/6 inhibitors such as palbociclib, abemaciclib, and ribociclib have demonstrated efficacy in advanced HR+/HER2- breast cancer. Drug-related toxicity has been manageable, but variable amongst the drugs. This meta-analysis was conducted to guide CDK inhibitor choice based on efficacy and toxicity. Methods: A systematic literature review of Pubmed, Cochrane Library, and EMBASE was performed in December 2018. Efficacy was evaluated via reported progression free survival (PFS) and pooled hazard ratios (HR). Overall response rate (ORR), treatment discontinuation, and treatment-related adverse events (AEs) were measured via pooled odds ratios (OR). Meta-analyses were performed using random effects modeling and 95% confidence intervals (CI). Results: A pooled analysis of 7 phase III clinical trials (n = 4415) demonstrated a HR of 0.55 (CI: 0.51-0.60) for PFS and an OR of 1.93 (CI: 1.54-2.42) for ORR. First-line treatment trials (n = 3020) pairing CDK 4/6 inhibitors with NSAI/tamoxifen had a HR of 0.56 (CI: 0.51-0.60) for prolonged PFS and an OR of 1.64 (CI: 1.39-1.95) for ORR. Second-line treatment trials (n = 1916) pairing CDK 4/6 inhibitors with fulvestrant had an HR of 0.54 (CI: 0.48-0.61) for prolonged PFS and an OR of 2.48 (CI: 1.57-3.90) for ORR. Palbociclib and ribociclib had similar rates of grade 3/4 AEs, neutropenia, and treatment discontinuation. Abemaciclib had lower rates of grade 3/4 AEs overall, but significantly increased rates of diarrhea and treatment discontinuation due to AEs. Conclusions: Each drug demonstrated a significant improvement in PFS. However, there is no statistical difference in efficacy among the three CDK inhibitors. Treatment decisions can be guided by the tolerability of AEs amongst the medications. Further patient follow-up will illuminate whether there is an OS advantage in this novel drug class. [Table: see text]