Clinical Impact of CDK4/6 Inhibitors in De Novo or PR- or Very Elderly Post-Menopausal ER+/HER2- Advanced Breast Cancers.

The CDK4/6 inhibitors significantly increase progression-free survival (PFS) in ER+/HER2- advanced breast cancer patients. In clinical trials, overall survival (OS) improvement has been demonstrated for ribociclib and abemaciclib but not for palbociclib. We undertook a real-world evaluation of PFS and OS in 227 post-menopausal patients who received first-line CDK4/6 inhibitors. There is no significant difference in median PFS (27.5 months vs. 25.7 months, p = 0.3) or median OS (49.5 months vs. 50.2 months, p = 0.67) in patients who received either palbociclib or ribociclib, respectively. De novo disease is significantly associated with prolonged median PFS and median OS compared with recurrence disease (47.1 months vs. 20.3 months ( p = 0.0002) and 77.4 months vs. 37.3 months ( p = 0.0003), respectively). PR- tumours have significantly reduced median PFS and OS compared with PR+ disease (19.2 months vs. 38 months ( p = 0.003) and 34.3 months vs. 62.6 months ( p = 0.02), respectively). In the very elderly (>80 years), median PFS and OS are significantly shorter compared with patients who are 65 years or below (14.5 months vs. 30.2 months ( p = 0.01), and 77.4 months vs. 29.6 months ( p = 0.009), respectively) in the palbociclib group. Our data suggest that the benefit in the very elderly is limited, and PR+/de novo disease obtains the maximum survival benefit.