2396P - Relationship of tumor fraction in circulating tumor DNA (ctDNA) with prognosis in patients with advanced urothelial cancer

Background

Advanced urothelial cancer (aUC) is often characterized by rapid symptomatic disease progression, making early disease control of particular importance. Development of immunotherapy has been particularly challenging due to limited disease control rates in unselected patients. A biomarker to identify patients with a better prognosis and slower tumor growth kinetics would be of significant clinical utility to personalize therapy. Circulating tumor DNA (ctDNA) is a promising biomarker in multiple tumor types including aUC. Recent work shows that a single time-point/measurement of ctDNA tumor fraction (TF) is prognostic in several other tumor types but has not yet been investigated in aUC.

Methods

This study used a cohort of patients in the de-identified Flatiron Health-Foundation Medicine urothelial clinico-genomic database, which originated from approximately 280 US cancer clinics (∼800 sites of care), who underwent ctDNA testing as part of routine care. TF calculation on FoundationOne®LiquidCDx was based on a composite algorithm incorporating multiple factors including aneuploidy, variant allele frequency, and canonical alterations. Patient/disease characteristics, laboratory and treatment data were captured from the electronic health record. Progression-free survival (PFS) and overall survival (OS) were evaluated by TF level while controlling for relevant covariables.

Results

83 patients with aUC were included. High ctDNA TF (≥1%) was associated with poor prognostic clinical features. High ctDNA TF also correlated with significantly reduced rwPFS in univariable analysis (hazard ratio (HR) 2.01, 1.14-3.56, p=0.01) and after correction for covariates (HR 2.37, 0.99-5.66, p=0.05). There was a trend towards shorter rwOS in univariable and multivariable analysis.

Conclusions

ctDNA TF is a prognostic biomarker in aUC with potential to inform expected longevity of patients. With further prospective validation, TF could be useful in predicting which patients with aUC have particularly aggressive disease and may enable personalized therapeutic decision-making.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors and Foundation Medicine.

Funding

Has not received any funding.

Disclosure

G. Li, A. Clark, R. P. Graf: Financial Interests, Personal, Full or part-time Employment: Foundation Medicine; Financial Interests, Personal, Stocks/Shares: Roche Holding AG. L. Pasquina, G. Oxnard: Financial Interests, Personal, Full or part-time Employment: Foundation Medicine; Financial Interests, Personal, Stocks or ownership: Roche Holding AG. All other authors have declared no conflicts of interest.