Abstract P4-07-20: Effect of prior treatments on post-CDK 4/6 inhibitor overall survival in hormone receptor positive breast cancer

Abstract Purpose: There are multiple treatment options for patients with metastatic breast cancer (MBC); however, there is minimal data on the optimal sequencing. Furthermore, limited information is available to understand the influence of prior treatment duration and class on novel therapies in real-world settings, such as cyclin-dependent kinase 4/6 inhibitors (CDK 4/6i) for patients with hormone receptor-positive, human epidermal growth factor receptor 2- negative (HR+ HER2-) MBC. Our study sought to identify the effect of prior treatments on post-CDK 4/6i survival. Methods: This retrospective study used the nationwide, de-identified electronic health record-derived Flatiron Health database of women with HR+ HER2- MBC who received at least one CDK 4/6i between 2011 and 2020. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated for the association between duration and class of all cancer treatments prior to receipt of CDK 4/6i and overall survival (OS) adjusting for age at diagnosis, race and ethnicity, site of metastasis, and metastatic diagnosis year. Time dependent HRs were used to compare the OS for patients receiving one versus multiple CDK 4/6i. Results: Of 5,363 patients, most were aged 55-64 (29%), White (69%), and had visceral metastasis (70%). The median survival from receipt of first CDK 4/6 inhibitor was 3.3 years. When compared to patients with no prior treatments, patients with up to one year of prior treatments had a 30% increased hazard of death ((HR, 1.30; 95% CI 1.15-1.46; Table 1). Similarly, patients with one to less than three years of prior treatment had a 68% increased hazard of death (HR 1.68; 95% CI 1.49-1.88) and those with three or more years had a 55% increased hazard of death (HR 1.55; 95% CI 1.36-1.76). Furthermore, patients who received prior endocrine therapy alone experienced a 29% increased hazard of death (HR, 1.29; 95% CI 1.16-1.44), while patients receiving prior chemotherapy experienced a 72% increased hazard of death (HR, 1.72; 95% CI 1.54-1.93) when compared with patients who did not receive a prior treatment. Finally, patients who received a different CDK 4/6i after their first had a 17% decreased hazard of death compared to patients who received subsequent endocrine or chemotherapy after their first CDK 4/6i (HR, 0.83; 95% CI 0.71-0.96). Conclusion: Prior treatment duration and class are associated with a decreased overall survival after CDK 4/6 inhibitor administration. However, patients receiving more than one CDK 4/6 inhibitor in their sequence saw survival benefits. This highlights the importance for clinicians to consider prior treatment and duration in treatment decision-making and for trialists to stratify by these factors when reporting results of future studies. Table 1: The association between OS and treatment duration and class before CDK 4/6 Citation Format: Jeffrey Franks, Nicole E. Caston, Ahmed Elkhanany, Travis Gerke, Andres Azuero, Gabrielle B. Rocque. Effect of prior treatments on post-CDK 4/6 inhibitor overall survival in hormone receptor positive breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-20.