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Background -The combination of CDK4/6 inhibitors and endocrine therapy (ET) is a standard firstline therapy for hormone receptor positive (HR+)/HER2-metastatic breast cancer (mBC). Preliminary data suggest that CDK4/6 inhibitors can alter the host immune function and stimulate tumor cell-directed immunity. However, clinical data are scarce, and no data exist about the impact of age and frailty on this phenomenon. Material and methods -This biomarker substudy of the RibOB trial (NCT03956654) evaluated the impact of ribociclib and letrozole on circulating immune cell subsets and protein markers in older ( 70 years) patients with HR+/HER2-mBC. Peripheral blood mononuclear cell subtyping and analysis of plasma immune response and checkpoint markers were performed using flow cytometry at baseline and after three months of ribociclib + ET. Frailty status was assessed at baseline using G8 score. Results -20 patients (median age: 76 years, range: 70-87 years), 8 considered fit (G8>14), and 12 frail (G8 14), were included. After three months of treatment, the immune subset composition showed significant increases in nave B-, T-regulatory (Tregs), and CD4+ T-cells, while memory B-cells and Tregs were significantly decreased. In addition, consistent upregulation was seen in costimulatory receptors CD27 and CD28. Plasma immune checkpoint markers B7.2 (CD86) and PD-1 were significantly decreased. The immune subset profiles of fit versus frail persons showed no statistically significant difference. Conclusions -The study shows that the combination of ribociclib and ET modulates the immune system in older patients, potentially reversing the age-related immunosenescence process by increasing nave T-cell and B-cell populations and decreasing memory populations.
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Lambrechts et al. (2024) studied this question.