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

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.

Real-World Experience among Elderly Metastatic Breast Cancer Patients Treated with CDK4/6 Inhibitor-Based Therapy

“…In terms of OS duration and adverse effects of CDK4/6 inhibitor-based therapy, there is far more agreement across several prior studies and the current study when comparing older and younger cohorts. In agreement with previous findings [28,45], the current study reports that there is no significant difference in OS between patients <70 and patients ≥70 receiving CDK4/6 inhibitor-based therapy either in the combined cohort or in the AI-treated cohort and that the older population experiences reduced OS in the FUL-treated cohort (Supplementary Figure S2).…”

“…This is despite the fact that elderly populations represent a large percentage of the newly diagnosed cases, with the majority of such cases being HR+ and HER2− presentations [20,21]. Recently, there has been an increased focus on specifically addressing the needs and outcomes of older breast cancer populations [22][23][24][25][26][27][28], with the European Society of Breast Cancer Specialists and the International Society of Geriatric Oncology recommending 70 years of age as an appropriate stratification point [29].…”