Association between the neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios and efficacy of CDK 4/6 inhibitors in advanced breast cancer: The observational multicenter Italian PALMARES study

Background Preclinical evidence indicates that Cyclin-Dependent Kinase 4/6 inhibitors (CDK 4/6i) stimulate antitumor immunity as part of their antineoplastic activity. The neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) are easy-to-measure indicators of systemic inflammation and immune system functional status. We investigated their association with CDK 4/6i efficacy in patients (pts) with hormone receptor-positive HER2-negative advanced breast cancer (HR+ HER2- aBC). Methods We conducted a retrospective, observational, multicenter Italian study to investigate the association between NLR or PLR, as measured at baseline and after the first 3 treatment cycles, and progression free survival (PFS) in HR+ HER2- aBC pts treated with CDK 4/6i plus endocrine therapies (ETs). The thresholds for NLR and PLR were defined through the maximally selected rank statistics. The impact of these parameters on PFS was evaluated at univariate and multivariable analysis by using Cox proportional hazard model. Results 308 pts were treated with palbociclib (n=256), ribociclib (n=39) or abemaciclib (n=13) plus ETs. Of them, 168 (54.5%) pts received CDK 4/6i as first-line, 88 (28.6%) as second-line, and 52 (16.9%) as third- or subsequent line of treatment for advanced disease between January 2017 and March 2020. With a median follow-up of 16.8 months (95% CI, 15.1-18.2), median PFS in the whole pt population was 17.1 months (95% CI, 14.6-25.0). At multivariable analysis, we found an independent association between high NLR or PLR and lower PFS, both when these parameters were evaluated at baseline (aHR 1.57, 95% CI 1.07-2.29, p=0.02 and aHR 1.97, 95% CI 1.29-3.02, p=0.002, respectively) and after the first 3 treatment cycles (aHR 2.73, 95% CI 1.37-5.46, p=0.005 and aHR 2.13, 95% CI 1.21-3.77, p=0.009, respectively). Conclusions This is the first study to show a significant association between high baseline or on-treatment NLR or PLR values and lower PFS in HR+ HER2- aBC pts. Although our results need prospective validation, they suggest that NLR and PLR could be used as precocious biomarkers of treatment efficacy.