Abstract 227P
Background
The prognostic impact of Cyclin-Dependent Kinase 4/6 inhibitors (CDK4/6i)-induced modulation of several peripheral blood cell counts (PBC) in patients (pts) with Hormone Receptor-positive (HR+), Human Epidermal growth factor Receptor 2-negative (HER2-) advanced breast cancer (aBC) has never been explored so far.
Methods
We conducted a multicenter, retrospective-prospective Italian study to investigate the impact of baseline or precocious on-treatment modifications (i.e., 2 weeks after therapy initiation) of PBC and their composite scores (CS) [neutrophils, monocytes, lymphocytes (lympho), platelets, NLR, MLR, PLR and PIV] on the progression-free survival (PFS) of pts with HR+HER2- aBC treated with endocrine therapies (ETs) plus the CDK4/6i palbociclib (pal), ribociclib or abemaciclib. Multivariable Random Forest and Cox Regression models were used to assess the independent association between PBC or CS and patient PFS.
Results
We evaluated 638 HR+ HER2- aBC pts treated with ETs plus CDK4/6i-based therapy as any line of treatment between January 2017 and May 2021 in six Italian Institutions. Median age was 61 years (IQR: 52-70); 83.1% of pts were post-menopausal, 72.8% had an ECOG PS of 0, 52.5% were in the first-line setting, 82.9% were treated with pal. Baseline lympho counts and their early on-treatment modulation were independently associated with PFS [median PFS (mPFS) 22.3 vs. 12.5 months for high vs low baseline lympho, respectively; adjusted Hazard Ratio (aHR) for lympho as a continuous variable: 0.78; 95% confidence intervals (CIs): 0.66-0.92; p=0.0144]. Moreover, pts with high baseline lympho counts and a lower decrease of lympho at 2 weeks had a mPFS of 24.6 vs. 11 months for pts with low baseline and higher decrease of lympho (aHR: 0.82; 95% CIs 0.73-0.93; p=0.0037). Other PBC and CS were not independently associated with PFS.
Conclusions
Baseline and early on-treatment modifications of peripheral blood lympho are independent predictors of clinical benefit from CDK4/6i in HR+/HER2- aBC pts. This study lays the foundations for implementing clinical strategies to boost antitumor immunity in HR+ HER2- aBC pts receiving ETs plus CDK4/6i.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
C. Vernieri: Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Other, Travel grant: Eli Lilly, Roche, Pfizer, Novartis, Istituto Gentili. G. Griguolo: Financial Interests, Personal, Funding: Novartis, Eli Lilly. E. Agostinetto: Financial Interests, Institutional, Advisory Role: Eli Lilly; Financial Interests, Institutional, Advisory Board: Sandoz; Financial Interests, Institutional, Other, support to attend medical conferences: Roche, Eli Lilly, Genetic, Istituto Gentili. G. Curigliano: Financial Interests, Institutional, Funding: AstraZeneca, Daiichi Sankyo, Merck; Financial Interests, Institutional, Other, Consulting: BMS, Roche, Pfizer, Novartis, Eli Lilly, AstraZeneca, Daiichi Sankyo, Merck, Seagen, Ellipsis; Financial Interests, Institutional, Other, Honoraria: Pfizer, Eli Lilly. D. Generali: Financial Interests, Other, Consulting or honoraria: Eli Lilly, Novartis, Pfizer, Roche, Istituto Gentili, Eisai. M.V. Dieci: Financial Interests, Personal, Invited Speaker: Eli Lilly, Pfizer; Financial Interests, Personal, Advisory Board: Novartis, Eli lilly, Seagen, Exact Science; Financial Interests, Personal, Other, Consultancy: Pfizer; Financial Interests, Institutional, Research Grant: Veneto Institute of Oncology IOV-IRCCS, Italian Ministry of health, University of Padova. All other authors have declared no conflicts of interest.