Abstract 300P
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.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
D.G. Generali: Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer. G. Curigliano: Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Honoraria (institution), Advisory/Consultancy: Novartis; Honoraria (institution), Advisory/Consultancy: lilly; Honoraria (institution), Advisory/Consultancy: Roche; Advisory/Consultancy: Ellipses Pharma; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Celltrion. G. Bianchi: Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Novartis. F.G.M. De Braud: Advisory/Consultancy: Tiziana Life Sciences; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Advisory/Consultancy, Research grant/Funding (institution): Celgene; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: Servier; Advisory/Consultancy: Pharm Research Associated; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Ignyta; Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen; Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy: Octimet Oncology; Advisory/Consultancy, Research grant/Funding (institution): Incyte; Speaker Bureau/Expert testimony: Pierre Fabre; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Gentili; Advisory/Consultancy: Dephaforum; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer; Advisory/Consultancy: Fondazione Menarini. All other authors have declared no conflicts of interest.