Abstract 294P
Background
Neutropenia (NP) is the main dose limiting toxicity of CDK4/6i. The present study aimed to evaluate the feasibility of a cfDNA-based workflow as a novel tool for assessing the risk of treatment-induced recurrent-neutropenia (rec-NP) and NP-induced CDK4/6i dose reduction (DR) in patients (pts) treated for luminal MBC.
Methods
A prospective cohort of 83 luminal MBC pts treated with first line ET and CDK4/6i in the CRO-2018-56 multicenter study was analyzed. cfDNA was characterized through droplet digital PCR (ddPCR) based on different ACTB DNA fragments lengths: short (s), medium (sl) and long (l). Blood samples were collected before treatment start (BL) and at the first clinical evaluation after 3 months (E1). Associations between clinical characteristics, cfDNA, rec-NP (≥3 NP events) and DR were explored through Kruskal Wallis.
Results
NP was higher than G2 in 46 out of 83 pts (55%). Overall, 29 pts (35%) developed rec-NP and 12 pts (26%) reduced CDK4/6i dose after NG3-G4. Notably, BL neutrophils count (Neu), WBC and lactate dehydrogenase (LDH) were significantly lower in pts that developed rec-NP (respectively p=0.0009, p=0.0008 and p=0.0375), while no significant associations with DR were observed. De novo metastatic pts had a lower risk of DR (p=0.0304) while pattern of metastasis was not associated with significant DR. BL ACTB_m was higher in pts that experienced DR (p=0.0096) while no associations emerged between ACTB_m and rec-NP. BL neu and ACTB_m were then combined to describe 4 distinct risk subgroups after dichotomization at the median value. Although pts with high ACTB_m and high neu did not experience any DRs, no significant differences were observed among subgroups (p=0.577).
Conclusions
The present study suggested that cfDNA can be used not only as a tumor-related biomarker in MBC, but also as a tool to assess the risk of drug-related adverse events, such as CDK4/6i-induced dose-limiting neutropenia. Additional investigations are planned to further refine the concept.
Clinical trial identification
CRO-2018-56.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Ricerca Finalizzata Italian Ministry of Health Ricerca Finalizzata Italian Ministry of Health.
Disclosure
L. Gerratana: Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Novartis; Non-Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Menarini Silicon Biosystems. F. Puglisi: Financial Interests, Advisory Role: Roche; Financial Interests, Advisory Role: Amgen; Financial Interests, Advisory Role: Lilly; Financial Interests, Advisory Role: Novartis; Financial Interests, Advisory Role: Pfizer; Financial Interests, Advisory Role: Elisai; Non-Financial Interests, Other, Travel, Accommodations, Expenses: Celgene; Non-Financial Interests, Other, Travel, Accommodations, Expenses: Roche; Financial Interests, Other, Honoraria: Roche; Financial Interests, Other, Honoraria: MSD; Financial Interests, Other, Honoraria: AstraZeneca; Financial Interests, Other, Honoraria: Novartis; Financial Interests, Other, Honoraria: Lilly; Financial Interests, Other, Honoraria: Pfizer; Financial Interests, Other, Honoraria: Pierre Fabre; Financial Interests, Other, Honoraria: Daiichi Sankyo; Non-Financial Interests, Funding: Eisai; Non-Financial Interests, Funding: AstraZeneca; Non-Financial Interests, Funding: Roche. All other authors have declared no conflicts of interest.