Ethnicity-based comparative analysis of treatment endpoints of 30,000 HR+/HER2− metastatic breast cancer patients on CDK4/6 inhibitors (palbociclib/ribociclib/abemaciclib).

Abstract

1085 Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i), in combination with endocrine therapy, are the mainstay for HR+/HER- metastatic breast cancer (MBC). However, ethnically diverse populations remain underrepresented in randomised clinical trials, limiting the ability to stratify by ethnicity. This meta-analysis utilises real-world evidence to compare treatment endpoints i.e., overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and adverse effects (AE) across ethnic groups. Methods: 116 studies from MEDLINE and Embase were included (Palbociclib: 67, Abemaciclib: 29, Ribociclib: 20). 31580 HR+/HER- MBC patients (Asian [AS]:22067; White [WH]: 8993; Black [BL]: 510) were included. Median survival and response rates were calculated using a random effects model to account for between-study variability. Parentheses represent 95% confidence intervals (CI). Results: Pooled analysis shows disparities in efficacy and significant variation in haematological toxicity. Maximum mOS benefit for AS was on palbociclib (61.8mo) whereas for WH was ribociclib (63.9mo), primarily driven by long-term follow-up in MONALEESA. mPFS benefit was longest in BL patients on abemaciclib (17mo), WH patients on palbociclib (27.7mo), AS patients on ribociclib (25.2mo). ORR was highest for ribociclib across all ethnic groups (Table). Meta-regression indicated ethnicity was not a significant independent moderator of AE risk (p > 0.05). AS cohorts demonstrated the highest incidence of Grade 3+ neutropenia across all agents: Palbociclib (72.0%; 49.5–87.1), Abemaciclib (52.8%; 46.1-59.4), and Ribociclib (45.8%; 39.1-52.5; p < 0.0001). In contrast, WH and BL patients exhibited significantly lower G3+ neutropenia rates, ranging from 12.0% to 33.8% (p < 0.0001). AS patients also showed the highest rates of leukopenia and anaemia across all CDK4/6i. Conclusions: Our large-scale meta-analysis findings establish a novel, evidence-based ethnicity-informed CDK4/6i selection framework to optimize treatment endpoints in HR+/HER2- MBC patients. This highlights the urgent need for prospective trials focused on underrepresented populations to close the survival gap. Metric Subgroup Palbociclib Abemaciclib Ribociclib ORR (%) AS 34.0 (27-42) 28.7 (16.1-41.3) 52.4 (46.4-58.5) WH 34.0 (28-65) 41.9 (14.9-68.9) 44.9 (32.1-57.7) BL 25.0 (17-23) N/A 34.6 mPFS (mo) AS 21.0 13.0 25.2 WH 27.7 21.8 24.1 BL 14.1 17.0 10.8 mOS (mo) AS 61.8 25.2 58.7 WH 60.5 37.6 63.9