1908P - Utility of circulating tumor (ct)DNA testing for molecular residual disease (MRD) detection and treatment response monitoring in patients (pts) with renal cell carcinoma (RCC)

Background

Increased heterogeneity in outcomes has been observed post nephrectomy in pts with RCC with standard clinical parameters being primarily used for risk assessment. Currently, no blood-based biomarkers are available that can predict recurrence or response to therapy. Herein, we demonstrate the utility of ctDNA in identifying MRD and assessing concordance with radiographic imaging in this pt population.

Methods

This real-world evidence-based multi-institutional study included a cohort of 82 pts with stages I-IV RCC who underwent nephrectomy (+/- metastasectomy), with 41 pts receiving adjuvant therapy (AT) (Table). Longitudinal ctDNA testing on post nephrectomy plasma samples (n=256) was performed using a tumor-informed ctDNA assay (Signatera^TM). ctDNA results were analyzed and association with clinical outcomes was assessed.

Results

In this cohort, the majority of the pts (75.6%; 62/82) were serially ctDNA negative and 91.9% (57/62; negative predictive value) of these showed no evidence of disease (NED) or non-progressive disease (partial response or stable disease) on imaging at the end of the follow-up. Longitudinal ctDNA detection was 24.3% (20/82; any time positivity) and 65% (13/20) of these demonstrated concordance between ctDNA status/dynamics and imaging. Among the 13 concordant pts, 53.8% (7/13) were ctDNA positive and relapsed, and among the remaining 7, 5 had insufficient imaging/ctDNA testing and 2 were discordant with positive ctDNA and NED on imaging. Table: 1908P

Patient demographics and clinical features (N=82)

*all 8 were stage IV patients

Conclusions

Overall, we demonstrate the utility of ctDNA testing for MRD detection. Future prospective studies in RCC would be needed to validate the utility of ctDNA in informing clinical decision-making.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Natera.

Funding

Natera.

Disclosure

S. Sudhaman: Financial Interests, Personal, Full or part-time Employment: Natera; Financial Interests, Personal, Stocks or ownership: Natera. C. Carson: Financial Interests, Institutional, Full or part-time Employment: Natera, Inc.. T. Mahmood, E.Z. White: Financial Interests, Personal, Full or part-time Employment: Natera; Financial Interests, Personal, Stocks/Shares: Natera. A. ElNaggar: Financial Interests, Personal, Full or part-time Employment: Natera; Financial Interests, Personal, Stocks or ownership: Natera; Financial Interests, Personal, Speaker, Consultant, Advisor: EMD Serano, GSK. M.C. Liu: Financial Interests, Institutional, Funding: Eisai, Exact Sciences, Genentech, Genomic Health, GRAIL, Menarini Silicon Biosystems, Merck, Novartis, Seattle Genetics, Tesaro; Financial Interests, Personal, Full or part-time Employment: Natera; Financial Interests, Personal, Stocks/Shares: Natera. R.R. McKay: Financial Interests, Personal, Speaker, Consultant, Advisor: Janssen, Novartis, Tempus, Exelixis, Pfizer, Bristol-Myers Squibb, Astellas Medivation, Dendreon, Bayer, Sanofi, Merck, Vividion, Calithera, AstraZeneca, Myovant, Caris Life Sciences, Sorrento Therapeutics, AVEO, Seattle Genetics, Telix, Eli Lilly; Financial Interests, Institutional, Funding: Pfizer, Bayer, Tempus. V. Margulis: Financial Interests, Personal, Speaker, Consultant, Advisor: Merck, Urogen, Janssen, Lantheus. W. Huang: Financial Interests, Institutional, Funding: Intuitive Surgical. All other authors have declared no conflicts of interest.