360P - Identification of circulating immune factors as predictive biomarkers of CDK4/6i treatment efficacy in advanced breast cancer

Background

Treatment for ER+/HER2- advanced breast cancer (ABC) has undergone a revolution with the approval of CDK4/6 inhibitors (CDK4/6i). There are no effective markers of treatment efficacy, although growing evidence points towards antitumor immune response. Here, we identify a group of blood immune factors that determine CDK4/6i efficacy and may be useful predictive biomarkers.

Methods

Luminex® technology was used to evaluate levels of soluble circulating factors in peripheral blood from 68 ER+/HER2- ABC patients treated with CDK4/6i at distinct time-points: prior to treatment initiation (Baseline), after 4-6 months under treatment (INT1) and at progression or last follow-up (PROG/INT2). Response was classified in good (GR) or poor (PR) based on hormone sensitivity and progression-free survival (PFS) according to data from pivotal studies. T-test comparisons were used to identify factors associated to each response group and Kaplan Meier and Cox regression models to assess association with survival.

Results

Twenty-nine distinct circulating blood factors, including pro- and anti-inflammatory cytokines, were first assessed in basal samples (n=20, 10 GR and 10 PR). Supervised hierarchical clustering of cytokine expression identified 3 distinct clusters differentially expressed depending on treatment efficacy. The most informative cytokines were selected for further testing in the extended cohort, together with soluble immune checkpoints (TIM-3, LAG-3, PD-1 and CTLA-4). In basal samples, low expression of IL-8 and TIM-3 were correlated with improved PFS (p=0,02 and p<0,001, respectively) and overall survival (OS, p=0,002 and p=0,001, respectively). Longitudinal analysis confirmed the predictive value of IL-8 at INT1 time-point (p=0,042). A similar tendency was also observed at INT1, indicating that low levels of LAG-3 and IL17A are associated with better PFS.

Conclusions

Plasma levels of IL8, IL17A, LAG-3 and TIM-3 may be reliable biomarkers for predicting CDK4/6i treatment efficacy in ABC. Although requiring further validation in clinical settings, the use of blood-based test with predictive value, may represent a useful tool to monitor CDK4/6i response.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Mireia Margeli.

Funding

Pfizer, ISCIII.

Disclosure

All authors have declared no conflicts of interest.