Abstract P4-12-14: Updated efficacy and safety of CDK4/6 inhibitors plus endocrine therapies in elderly HR+/HER2- metastatic or advanced breast cancer: patient-level network meta-analysis

Abstract Background: Breast cancer (BC) is the most common cancer in women worldwide. More than 80% of invasive BCs cases are newly diagnosed among women aged 50 years or older, and mainly present with an estrogen receptor ER-positive and HER2-negative subtype disease. About 91% of deaths occur in this age population. Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors showed a significant increased survival benefits in terms of progression-free survival and overall survival (OS), but the evidence on treating older women with metastatic BC is limited. Therefore, we comprehensively evaluated the efficacy and safety of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy (ET) in older women with HR+/HER2- metastatic or advanced BC.Methods: We comprehensive search on PubMed and EMBASE database from Jan 2018 to Dec 2024 for phase II or III randomized controlled trials (RCTs) investigating modality treatments for HR+/HER2- metastatic or advanced BC. Kaplan–Meier curves for progression-free survival (PFS) and overall survival (OS) were reconstructed to retrieve individual patient-level data to strengthen the comparison of the benefits of all modality treatments of interest. Each study was pooled in a fixed-effects or randomized-effects model based on the individual study quality in this network meta-analysis (NMA). We also performed a subgroup analysis and reported the incidence of ≧grade 3 adverse events in elderly patients (≧65 years). The primary endpoint was pooled PFS, OS and the comparable safety. The modality treatments were ranked using SUCRA scores.Results: We identified 10 phase II and III randomized controlled trials with 7 modality treatments that met the inclusion criteria. Among them, 1823 patients with PFS and 2132 patients with OS results were included in the analysis. In terms of PFS, ribociclib+letrozole (Let) ranked highest among all other treatment modalities, followed by palbociclib+fulvestrant(ful). For OS, palbociclib plus ful is the best treatment compared to other treatment options of interest. The ranking probabilities of palcociclib plus fulvestrant (97.52%) and ribociclib plus let had the highest probability of achieving superior OS and PFS (90.89%) for elderly women with mBC. In terms of safety, palbociclib plus endocrine (letrozole or fulvestrant) (55.7%), abemaciclib plus letrozole or fulvestrant (28.7%) were associated with relatively high ≧grade 3 adverse events (AE) compared to placebo plus endocrine therapy. Ribociclib plus Let (15.2%) had a relatively lower rate of ≧ grade 3 adverse events (AEs) than the other two CDK4/6 inhibitors.Conclusion: Ribociclib plus letrozole is considered effective for PFS and a relatively safe treatment option for older women with HR+/HER2- subtype metastatic or advanced BC. However, given the limited reliable evidence, comprehensive and well-designed randomized controlled trials with a large sample size are needed to confirm our results. Citation Format: Yun-Sheng Tai, Henry, WC Leung, Shyh-Yau Wang. Updated efficacy and safety of CDK4/6 inhibitors plus endocrine therapies in elderly HR+/HER2- metastatic or advanced breast cancer: patient-level network meta-analysis [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P4-12-14.