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

SIMPLE SUMMARY: The cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors palbociclib, ribociclib and abemaciclib have transformed the lives of patients with ER+/HER2− metastatic breast cancer (MBC). Clinical trials have shown that all three CDK4/6 inhibitors improve progression-free survival (PFS), but only ribociclib and abemaciclib improve overall survival (OS). The data have generated debate in the oncology community as to which CDK4/6 inhibitor to use in routine clinical practice. In this context, real-world data in a heterogeneous population of advanced breast cancer patients can inform clinical decision-making. Here, in a cohort of 227 patients, we show that palbociclib and ribociclib have similar PFS and OS benefits in the real world. Our data should reassure oncologists that both palbociclib and ribociclib remain effective treatment options for patients. ABSTRACT: 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.