Patterns of Disease Progression in Advanced Breast Cancer Patients Treated With Cyclin D Kinase 4/6 Inhibitors: Prognostic and Therapeutic Implications

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INTRODUCTION: To study the patterns of progression (POP) in hormone receptor-positive (HR+), human epidermal growth receptor 2-negative (HER2-) advanced breast cancer (aBC) treated with cyclin D kinase inhibitor (CDK 4/6i) and analyze their impact on prognosis and subsequent treatment. PATIENTS AND METHODS: We retrospectively investigated patients with HR+ HER2- aBC with progressive disease after CDK4/6i treatment at our center from 2016 to 2020. Based on European Society for Radiotherapy and Oncology (ESTRO)/European Organization for Research and Treatment of Cancer (EORTC) consensus, patients were divided into 4 groups: repeat oligoprogression (RO, oligoprogression with a history of oligometastatic disease), induced oligoprogression (IO, oligoprogression with a history of polymetastatic disease), collectively oligoprogressive disease (OPD), de novo polyprogression (DP, polyprogression with a history of oligometastatic disease), and repeat polyprogression (RP, polyprogression with a history of polymetastatic disease)-together diffusely progressive disease (DPD). Kaplan-Meier survival analysis was used for time-to-event data. RESULTS: Among the 151 patients, 47 (31%) had OPD, including 33 (22%) with RO and 13 (9%) with IO. Similarly, 104 (69%) patients had DPD, including 93 (61%) with RP and 12 (8%) with DP. The 1-year next-line progression-free survival (nPFS) was 60.5% in the IO group, 42.9% in the RO group, 30.3% in the DP group, and 26% in the RP group (P = .01). The 3-year overall survival (OS) was also significantly different (84% vs. 79% vs. 66% vs. 39%, P = .02). The continuation of CDK4/6i beyond oligoprogression did not lead to worse outcomes (6-month nPFS, 69.9% vs. 73.7%, P = .07). CONCLUSION: The 4 distinct POP after CDK 4/6i treatment have prognostic value, and in this small but relevant cohort of patients, continuation of CDK 4/6i appears to be safe in those with IO.

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