Clinical efficacy and safety of front-line CDK4/6 inhibitor therapy in HR+/HER2- advanced breast cancer patients with visceral metastases: A retrospective study.

e13074 Background: The introduction of CDK4/6 inhibitors (CDK4/6i) has significantly improved the prognosis of patients with hormone receptor-positive, HER2-negative metastatic breast cancer (HR+/HER2- MBC). Despite these advances, many HR+/HER2- MBC patients still experience disease progression, particularly those with visceral metastases or endocrine resistance. Managing these high-risk subgroups remains a critical challenge in improving patient outcomes. Methods: This single-center, retrospective real-world study included 244 HR+/HER2- MBC patients with visceral metastases, who received frontline (1st-2nd line) CDK4/6i combined with endocrine therapy (ET) between January 2022 and August 2024. Progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety were evaluated. Results: The overall mPFS was 29.4 months (95% CI: 22.2-37.0 months), with an ORR of 48.8% and a DCR of 96.3%. Subgroup analysis showed better prognosis in patients with lung metastases (mPFS = 42.1 months). Multivariate analysis confirmed adjuvant chemotherapy as an independent prognostic risk factor and demonstrated that CDK4/6i combined with exemestane significantly reduced the risk of disease progression or death (HR = 0.475, P = 0.017). Additionally, both endocrine-sensitive and endocrine-resistant patients showed therapeutic response to CDK4/6i combined with ET. Patients receiving sequential chemotherapy followed by CDK4/6i also achieved favorable clinical benefit. Hematologic toxicity was the most common adverse events (AEs), but overall safety was manageable. Conclusions: This study provides valuable real-world evidence on the efficacy of CDK4/6i combined with ET in HR+/HER2- MBC patients with visceral metastases, with or without endocrine resistance. Future research could explore optimizing ET selection with CDK4/6i and improving AE management to support better therapeutic outcomes.