Abstract C015: FGFR1 and RB1 genetic alteration impair clinical benefit of CDK4/6 inhibitors plus endocrine therapy in HR+/HER2- advanced breast cancer

Abstract

Abstract Background: One of the great challenges for HR+/HER2- advanced breast cancer (ABC) is to determine who respond poorly to cyclin-dependent kinase 4/6 inhibitors (CDK4/6i). Chemotherapy is still used in HR+/HER2- patients. We aimed to explore cfDNA biomarkers for CDK4/6i plus endocrine therapy (ET), and compare its efficacy with chemotherapy in subgroups stratified by clinical and cfDNA characteristics. Method: Patients diagnosed with HR+/HER2- advanced breast cancer underwent first-line CDK4/6i plus ET or chemotherapy in Peking University Cancer Hospital from January 2018 to June 2022 were enrolled in this study. Baseline blood samples of patients were collected before first-line treatment for cfDNA sequencing. Results: Among all the 125 patients included in this study, the median PFS (mPFS) of CDK4/6i plus ET group (n=51) was significantly longer than patients treated with chemotherapy(n=74) (22.0 vs. 16.0 months, P = 0.025). In multivariate analysis, RB1 loss (Hazard ratio [HR] = 6.4, adjusted P = 0.031), FGFR1 gain (HR: 4.9, adjusted P = 0.030) were associated with shorter PFS of patients treated with CDK4/6i plus ET. A better efficacy of CDK4/6i plus ET was observed in patients with visceral metastasis, higher Ki-67 (≥20%) and smaller SLD (< 35mm) than chemotherapy. In subgroup analysis, interaction effects were found between RB1 loss (P interaction = 0.028), FGFR1 gain (P interaction = 0.004) and first-line treatment. Conclusion: This study revealed that FGFR1 gain and RB1 loss are independent prognostic factors for PFS of CDK4/6i plus ET, and chemotherapy was not superior to CDK4/6i plus ET in the absence of FGFR1 gain and RB1 loss, which might improve selection of patients for CDK4/6 inhibitors. Citation Format: Jianxin Zhong, Bin Shao, Hanfang Jiang, Huiping Li. FGFR1 and RB1 genetic alteration impair clinical benefit of CDK4/6 inhibitors plus endocrine therapy in HR+/HER2- advanced breast cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C015.