Efficacy and safety profiles of CDK4/6 inhibitor in patients with hormone receptor–positive and human epidermal growth factor receptor 2–negative (HR+/HER2−) advanced breast cancer (ABC) from the high-altitude versus low-altitude regions: A multi-center retrospective study.

Abstract

e13033 Background: Hypoxia in the high-altitude regions may alter the pharmacokinetic properties of anti-tumor drugs, including CDK4/6 inhibitors (CDK4/6i). CDK4/6i represents the optimal first-line (1L) treatment for hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC). The study is amied to assess clinical efficacy and safety profiles of CDK4/6i from first-line (1L) to third-line (3L) in patients with HR+/HER2- ABC from high-altitude versus low-altitude regions. Methods: Breast cancer patients who received CDK4/6i were enrolled from four cancer centers in China, including National Cancer Center (NCC), Chinese PLA General Hospital, and Peking University Cancer Hospital & Institute, and Qinghai University Affiliated Hospital. Suvival benefits and adverse events (AEs) were compared between high-altitude and low-altitude groups. Survival differences were analyzed via the Kaplan-Meier method and the log-rank test. Results: A total of 401 patients were eligible for the study, involving 294 from the low-altitude group, and 107 from the high-altitude group. In the 1L, objective response rate (ORR, 23.7% versus 5.3%, p=0.01), clinical benefit rate (CBR, 88.1% versus 57.9%, p<0.0001) and median progression-free survival (PFS, 42.1 months versus 15.2 months, p=0.001) in the low-altitude group were superior to high-altitude group. In the second-line treatment, CBR in the low-altitude group was higher (87.5% versus 48.0%, p=5.3E−4). ORR (20.8% versus 4.0%, p = 0.08) and PFS (15.8 months versus 8.2 months, p=0.11) were not significantly different. In the 3L settings, no significance was observed in PFS (5.2 months versus 5.8 months, p=0.45), ORR (16.5% versus 21.1%, p=0.74), and CBR (47.1% versus 47.4%, p=1). The most common AE was leukopenia (79.3%). The incidence of anemia (43.0% versus 29.6%, p=0.02) and thrombocytopenia (30.8% versus 20.4%, p=0.03) occurred more frequently in the high-altitude group. Conclusions: Patients with HR+/HER2- ABC in the high-altitude region developed inferior survival outcomes and individual tolerance to CDK4/6i, which might provide insights for optimizing the management of CDK4/6i in Chinese patients with HR+/HER2- ABC.