Real-World Outcomes Of Cyclin-Dependent Kinase Inhibitors Continued Beyond First Disease Progression In Hormone Receptor-Positive Metastatic Breast Cancer

CDK4/6 inhibitors (CDKis) are United States Food and Drug Administration-approved with endocrine therapy (ET) for hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. The benefit of continuing CDKi beyond first disease progression (PD) with CDKi/ET therapy is unknown. This retrospective study evaluated effectiveness of continuing CDKi/ET beyond first PD (n = 30). The median progression-free survival was approximately 12 months, suggesting that CDKi may remain efficacious beyond first PD.Background: CDK4/6 inhibitors (CDK4/6i), in combination with aromatase inhibitors, are United States Food and Drug Administration-approved for the treatment of hormone receptor-positive (HER+)/human epidermal growth factor receptor 2-negative (HER2(-)) metastatic breast cancer (MBC). The effectiveness of continuing them beyond first disease progression (PD) is currently unknown. This retrospective study evaluated the impact of the continuation of CDK4/6i beyond first PD in HR VHER2 MBC using real-world experience. Patients and Methods: A single-institution retrospective review of patients with HR+ MBC who received CDK4/6is from 2015 to 2018 and where CDK4/6is were continued beyond first PD. The primary outcome was progression-free survival (PFS) after initial PD on CDK4/6i therapy. Results: Thirty women with HR+/HER2(-) MBC met eligibility criteria. Patients were identified from a prospective database of patients at the Cleveland Clinic Foundation who were prescribed CDK4/6is. The median age and follow-up duration were 47.5 years and 27 months, respectively. Most patients received palbociclib (PA)/letrozole as initial therapy (67%), followed by PA/fulvestrant (23%), and PA/other aromatase inhibitor (20%), and abemaciclib with either fulvestrant or letrozole (6%). As of January 31, 2019, 25 (83.3%) patients were still alive, and 19 (63%) patients had progressed. The estimated median PFS for continued CDK4/6i use beyond the first PD was 11.8 months (95% confidence interval, 5.34-13.13 months). Conclusions: Among a small cohort of patients with HR+ MBC in a non-clinical trial setting, continuation of CDK4/6i-endocrine treatment post initial PD was associated with a median PFS of about 12 months. Formal randomized clinical trials evaluating the continuation of CDK4/6is beyond the first PD are currently ongoing and will provide more answers to this important clinical question. (C) 2020 Elsevier Inc. All rights reserved.