pstrongIntroduction./strongnbsp;Breast cancer is the most common malignancy in women and a leading cause of cancer mortality. The HR-positive/HER2-negative subtype accounts for most cases and is characterized by initial endocrine sensitivity followed by resistance. This study aimed to map and interpret randomized clinical trial evidence on the efficacy and safety of CDK4/6 inhibitor-based treatment strategies across different clinical settings in HR-positive/HER2-negative breast cancer.br /strongMethods. /strongA scoping review of randomized phase II/III trials (2015ndash;2025) was conducted using PubMed/MEDLINE and manual reference screening. Studies evaluating palbociclib, ribociclib or abemaciclib with endocrine therapy were included if reporting PFS, OS or iDFS.br /strongResults. /strongTwenty-two randomized trials were included, covering first-line metastatic, later-line, post-CDK4/6 progression and adjuvant settings. CDK4/6 inhibitors consistently improved PFS, with the most robust benefit in first-line and endocrine-resistant disease. OS benefit was demonstrated in several trials, particularly with ribociclib and abemaciclib, though results were heterogeneous. Evidence on optimal sequencing and post-progression strategies remains limited. In the adjuvant setting, benefit was not uniform: positive results for abemaciclib and ribociclib but not for palbociclib.br /strongConclusion./strong CDK4/6 inhibitors are a cornerstone of treatment in HR-positive/HER2-negative breast cancer. However, unresolved questions include optimal sequencing, management after progression, and predictive biomarkers. Future research should focus on biomarker-driven and individualized strategies based on tumor biology and disease dynamics./p
Gagović et al. (Tue,) studied this question.