KEY TAKEAWAYS
- The study aimed to compare the effectiveness and safety of CET vs PET in HR+/HER2- advanced breast cancer.
- The primary endpoints were to determine OS and PFS.
- CET showed superior survival benefits but was associated with higher rates of AEs, particularly hematologic ones.
The role of Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in combination with endocrine therapy (ET) to improve survival outcomes, particularly overall survival (OS), in patients with hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer remains uncertain. This issue is a subject of ongoing clinical debate.
Cailu Luo and the team aimed to compare the antitumor efficacy and adverse effects (AEs) of CDK4/6 inhibitors combined with ET (CET) versus placebo plus ET (PET).
Researchers searched 7 databases to find eligible studies, focusing on Phase III randomized control trials (RCTs) that compared CET to PET. They examined OS and progression-free survival (PFS) as the primary outcomes.
They also considered secondary outcomes, such as patient responses and any AEs that were reported. This approach helped them analyze the effectiveness and safety of CET compared to PET.
The results included 7 RCTs (DAWNA-2, MONALEESA-2, MONALEESA-3, MONALEESA-7, MONARCH-3, PALOMA-2, PALOMA-4). Patients in the CET group showed significantly better OS (HR: 0.81 [0.74, 0.88]), PFS (HR: 0.57 [0.52, 0.63], objective response rate (RR: 1.31 [1.20, 1.43]), and clinical benefit rate (RR: 1.11 [1.07, 1.15]).
While these benefits were seen across most subgroups, the CET group also had higher rates of total, grade 3-5, and serious AEs. The top grade 3-5 AEs were neutropenia (59.39%), leukopenia (24.11%), reduced white blood cell count (12.99%), hypertension (7.03%), and increased alanine aminotransferase (5.91%).
The study concluded that CET is superior to PET in HR+/HER2- advanced breast cancer, demonstrating enhanced survival and response rates. However, the increased incidence of AEs, particularly hematologic ones, necessitates careful monitoring and management in clinical practice.
The study was funded by the Natural Science Foundation of Jiangxi Province.
Source: https://pubmed.ncbi.nlm.nih.gov/39169295/
Luo C, Yu K, Luo X, et al. (2024). “CDK4/6 inhibitors plus endocrine therapy vs. placebo plus endocrine therapy for HR+/HER2- advanced breast cancer: a phase III RCTs based meta-analysis.” BMC Cancer. 2024;24(1):1031. Published 2024 Aug 21. doi:10.1186/s12885-024-12782-w
