Abstract 11P
Background
Liquid biopsy (LB) provides valuable molecular insights in metastatic breast cancer (MBC). This study examines the relationship between the highest VAF (hVAF) in ctDNA and patient survival outcomes.
Methods
In this retrospective analysis, the Guardant360 genomic assay, encompassing 74 genes and microsatellite instability status, was used on plasma samples prospectively collected at tumor progression from patients with MBC treated at Hospital Clinic of Barcelona. The hVAF for each patient was identified for analysis. Cox proportional hazards models assessed hVAF both as a continuous variable and in tertiles, focusing on its association with overall survival (OS). Multivariable analyses adjusted for menopausal status, performance status, bone-only disease, visceral disease, treatment line and cancer subtype was performed. For hormone receptor-positive(HR+)/HER2-negative(-) MBC treated after LB with endocrine therapy+CDK4/6 inhibitors (ET+CDK4/6i), hVAF's association with progression-free survival (PFS) was also explored.
Results
Between February 2021 and April 2022, 99 plasma samples from 99 patients were analyzed (median age: 59.7; 75.8% HR+/HER2-, 16.2% triple negative, 8.1% HER2+ MBC). Overall, ctDNA was detected in 98.0% of cases, with 94.0% showing pathogenic variants (PVs). The median number of PVs was 3 per patient (range: 1-16) and the most frequently mutated genes were TP53 (50;50.5%), ESR1 (38;38.4%) and PIK3CA (28;28.3%). Median follow-up was 27.2 months (0.56-37.45). OS was significantly different across hVAF tertiles (T3, T2 and T1 median OS [mOS] in months 13.1, 25.1 and NR; p<0.001). Higher hVAF significantly correlated with poorer OS both as continuous (hazard ratio [HR] 1.02, p<0.001) and categoric (HR T1 vs. T3: 3.76, p<0.001) variable. Multivariable analysis confirmed hVAF as an adverse prognostic factor (HR: 1.02, p=0.002). Continuous hVAF was negatively associated with PFS (HR: 1.05, p=0.007) in 24 patients under ET+CDK4/6i.
Conclusions
This study reveals hVAF significantly impacts OS in MBC patients, suggesting its potential for refining prognostic stratification in clinical trials and guiding the selection of which patients might benefit from more aggressive therapies in subsequent lines.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
I. Garcia Fructuoso: Financial Interests, Personal, Invited Speaker, And travel expenses: Novartis; Financial Interests, Personal, Invited Speaker, And Travel expenses: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Other, Travel expenses: Gilead, Lilly. O. Martínez-Sáez: Financial Interests, Personal, Invited Speaker: Novartis, Eisai; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Other, Travel expenses: Roche; Financial Interests, Personal, Other, Medical advisory: Reveal Genomics. E. Segui Solis: Financial Interests, Personal, Invited Speaker: Novartis, Veracyte, Pfizer, Daiichi Sankyo, Eisai; Financial Interests, Personal, Advisory Board: Pfizer, Seagen; Financial Interests, Personal, Full or part-time Employment: SOLTI; Financial Interests, Personal, Research Grant: Amgen. F. Schettini: Financial Interests, Personal, Invited Speaker: Novartis, Gilead, Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Other, Travel expenses: Novartis, Gilead, Daiichi-Sankyo. T. Pascual: Financial Interests, Personal, Invited Speaker: Pfizer/ AstraZeneca / Veracyte / Novartis; Financial Interests, Personal, Advisory Board: Roche/Genentech, Novartis. M. Munoz: Financial Interests, Personal, Expert Testimony: Roche, Novartis; Financial Interests, Personal, Other, International conference travel grants: Roche, Pfizer, Lilly, Gilead; Financial Interests, Personal, Advisory Board: Pierre Fabre, Seagen, AstraZeneca. A. Prat: Financial Interests, Personal, Invited Speaker: Roche, 1TRIALSP, S.L.; Financial Interests, Personal, Invited Speaker, Lecture fees: Novartis, Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Novartis, Pfizer, Oncolytics Biotech, Guardant Health, Peptomyc; Financial Interests, Institutional, Invited Speaker, Clinical trials: Daiichi Sankyo; Financial Interests, Institutional, Other, Contracted research: Boehringer, Medica Scientia inno. Research; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Member of Board of Directors, Leadership role: Reveal Genomics, SL.; Financial Interests, Personal, Stocks/Shares: Reveal Genomics, Oncolytics Biotech; Financial Interests, Personal, Royalties: Reveal Genomics, International Oncology Bureau, S.L.,; Financial Interests, Institutional, Invited Speaker: Roche, AstraZeneca, Novartis; Financial Interests, Personal and Institutional, Invited Speaker: Daiichi Sankyo; Non-Financial Interests, Institutional, Other, Leadership roles: Patronage committee: SOLTI Foundation, Actitud Frente al Cáncer Foundation; Non-Financial Interests, Personal, Other, Asociación Española de Investigación sobre el Cáncer: ASEICA. F. Brasó-Maristany: Financial Interests, Personal, Full or part-time Employment, part time employment: Reveal Genomics SL; Financial Interests, Personal, Other, Patents filed: EP23382703 and EP23383369: Reveal Genomics SL; Financial Interests, Personal, Other, Patents filed: PCT/EP2022/086493, PCT/EP2023/060810: Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer. M.J. Vidal Losada: Financial Interests, Personal, Advisory Board: Novartis/Pfizer, Roche, Pfizer, AstraZeneca/Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Novartis/Pfizer, Roche/Genentech, AstraZeneca/Daiichi Sankyo, Gilead Sciences, Veracyte, Guardanthealth; Financial Interests, Personal, Other, Travel, Accommodations, expenses: Pfizer; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Gilead Sciences. All other authors have declared no conflicts of interest.