Background: CDK 4/6 inhibitors with Endocrine therapy (ET) are the preferred first line treatment for Hormone Receptor positive and Human Epidermal Growth factor receptor 2 negative (HR+/HER2-) MBC. Over the last few years multiple trials have shown benefit in PFS. Only two studies evaluating Ribociclib and Abemaciclib showed an OS benefit while no statistically significant OS benefit has been reported in any of the studies evaluating Palbociclib raising the possibility that this benefit may be drug specific rather than applicable to all CDK 4/6 Inhibitors. This updated meta-analysis of randomized controlled trials (RCTs) aims to assess the PFS and OS of all three CDK 4/6 inhibitors in HR+/HER2- MBC. Methods: We performed a systematic search for RCTs using Cochrane Library, PubMed, Embase, and Web of Science. Only the phase II and III RCTs comparing CKD 4/6 inhibitors plus ET with ET alone were eligible for this meta-analysis. The pooled analysis of Hazard Ratio (HR) was performed with Review Manager 5.3 using random effect model. Results: A total of 8 RCTs including 4338 patients with HR+/HER2- MBC were included in this meta-analysis (table). The pooled HR for PFS was 0.55 (95% confidence interval (CI), 0.50-0.59; P< .00001) and the pooled HR for OS was 0.75 (95% CI, 0.68-0.84; P< .00001). Conclusions: The result of our meta-analysis confirms the previously reported PFS benefit from CDK 4/6 inhibitors plus ET and shows an OS benefit when including RCTs of all 3 CDK 4/6 inhibitors for the treatment of HR+/HER2- MBC.

(NSAI: Non steroidal aromatase inhibitor; Palbo: Palbociclib; Let: Letrozole; Ful:Fulvestrant; Ribo: Ribociclib; Abem: Abemaciclib; P: Placebo)