Background: In phase III studies, the CDK4/6-inhibitors palbociclib, ribociclib, and abemaciclib all have demonstrated similar clinical efficacy in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer (MBC) with regards to the primary endpoint of progression-free survival (PFS). However, the lack of overall survival (OS) benefit in the PALOMA-2 study is inconsistent with the OS benefit seen with the other two CDK4/6-inhibitors. This study sought to elucidate indirect treatment survival outcomes between CDK4/6-inhibitors in this setting. Methods: Phase III randomized controlled trials comparing first-line aromatase inhibitor with or without a CDK4/6-inhibitor in post-menopausal patients with HR+/HER2- MBC. A graphical reconstructive algorithm was utilized to retrieve patient level time-to-event data from reported Kaplan-Meier OS and PFS curves. Survival analyses were conducted with Cox proportional hazards model with a shared-frailty term incorporated to account for inter-study differences. Two-stage indirect treatment comparison model was conducted as a sensitivity analysis. Results: Three randomized phase III trials – PALOMA-2, MONALEESA-2 and MONARCH-3 – comprising 1,827 patients were included. Indirect pairwise comparison of all CDK4/6-inhibitor showed no significant PFS differences across one-stage and two-stage models (all p>0.05). Likewise, indirect treatment comparison between ribociclib vs palbociclib (one-stage: HR=0.903, 95%-CI: 0.746-1.094, p=0.297), abemaciclib vs palbociclib (one-stage: HR=0.843, 95%-CI: 0.690-1.030, p=0.094) and abemaciclib vs ribociclib (one-stage: HR=0.933, 95%-CI: 0.753-1.157, p=0.528) failed to demonstrate a significant OS difference. Conclusions: Findings from this indirect treatment comparison suggest no significant PFS or OS differences between CDK4/6-inhibitor agents when combined with an aromatase inhibitor in post-menopausal patients with HR+/HER- MBC.

HR, hazard ratio; CI, confidence interval.