The association of hormone receptor expression level and clinical efficacy of CDK4/6 inhibitor in hormone receptor-positive, HER2-negative metastatic breast cancer.

Kelvin K. H. Bao Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, Hong Kong info_outline Kelvin K. H. Bao, Carol HY Wong, Jackie Yung, Venus Tam, Ka Man Cheung, Jeffrey CH Chan, Harry HY Yiu

Authors Kelvin K. H. Bao Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, Hong Kong info_outline Kelvin K. H. Bao, Carol HY Wong, Jackie Yung, Venus Tam, Ka Man Cheung, Jeffrey CH Chan, Harry HY Yiu Organizations Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, Hong Kong Abstract Disclosures Research Funding No funding sources reported Background: In patients with hormone receptor-positive, HER2-negative metastatic breast cancer (HR+ HER2- MBC), the correlation between the level of expression of HR and the clinical efficacy of CDK4/6 inhibitors remains undefined. Methods: We identified consecutive patients with HR+ HER2- MBC starting a CDK4/6 inhibitor (palbociclib, ribociclib or abemaciclib) plus either an aromatase inhibitor or fulvestrant between Jan 2018 - Oct 2023 from an institutional cancer registry. Expression level of HR was stratified as high (H) (Allred score 7-8), moderate (M) (Allred score 5-6) or low (L) (Allred score 3-4) for both estrogen (ER) and progesterone receptors (PR). Patients were evaluated from start of treatment to December 2023, last visit or death, whichever came earlier. Median progression-free survival (mPFS) and overall survival (mOS) were endpoints. We evaluated the association of HR expression levels with mPFS and mOS using log-rank test and multivariate Cox regression modelling. Results: We examined data from 436 women with HR+ HER2- MBC. Median age at treatment was 60.5 yr. Majority of patients received the treatment in the first-line setting (72.5%), with palbociclib (54.1%), ribociclib (31.9%) and abemaciclib (14.0%) as the CDK4/6 inhibitor. In the population that received first-line treatment, ER expression levels were H (83.5%), M (11.4%) and L (5.1%) respectively. ER expression levels were strongly associated with mPFS and mOS. For ER H, M and L expressions, mPFS were 29.4m, 9.2m and 2.9m ( p<0.001 ); mOS were 52.1m, 40.6m and 11.6m ( p<0.001 ), respectively. In multivariate analysis, ER expression levels remain strongly predictive for both mPFS and mOS after adjustment for clinicopathological risk factors (ER L vs H, mPFS HR 10.6, p<0.001 ; mOS HR 4.66, p<0.001 ; ER M vs H, mPFS HR 4.90, p<0.001 ; mOS HR 2.06, p=0.05 ). Findings were similar for the second line and beyond population. In the ER-high expression cohort, the PR expression levels also correlate strongly with treatment efficacy and survival, with mPFS of 40.8m, 24.5m, 24.0m, 14.1m ( p<0.001 ) and mOS of NR, 53.3m, 48.1m, 26.9m ( p<0.001 ) respectively for PR H, M, L and zero expressions. Conclusions: In this real-world cohort of patients with HR+ HER2- MBC, we observed that the semi-quantitative HR expression level subgrouping is a strong predictor for the efficacy of treatment with CDK4/6 inhibitors. In contrast to patients with high HR expression levels, the small population with ER-low expression derived very limited benefits from the standard endocrine therapy with CDK4/6 inhibitors. Our findings provided a practical tool to guide the selection of the appropriate systemic therapy for individual patients.