IBCN 2018: Association of Circulating Tumor -DNA Genomic Alterations with Outcomes in Metastatic Urothelial Carcinoma

Rotterdam, The Netherlands (UroToday.com) Petros Grivas studied if circulating Tumor -DNA genomic alterations (ctDNA GA) correlated with outcomes and signified therapy targets. Patients with urothelial carcinoma (UC) who underwent ctDNA analysis for potentially actionable GA via Guardant360 were identified. A 73-gene ctDNA next generation sequencing (NGS) panel from CLIA-licensed, CAP-accredited laboratory (Guardant Health, Inc.) offers complete exon sequencing in 19 cancer genes, critical exons in 54 genes, amplifications (18 genes), fusions (6 genes) & indels (23 genes) from 10 mL of peripheral blood.

KM method was used to estimate overall survival and failure-free-survival since therapy initiation. Cox proportional hazards regression was used to assess the association of ctDNA GA present in > 10% of pts and clinical factors with OS and FFS in univariable analyses. All tests were 2-sided, p ≤0.05 was significant. We also evaluated GA in serial samples to assess genomic evolution.

A total of 557 patients with 673 samples were analyzed; 603 samples had ctDNA detected; most commonly altered genes were TP53, ARID1A, ERBB2, PIK3CA. 124 pts had available clinical data, of whom 65 had received prior platinum, 21 prior taxane and 10 prior PD1/PD-L1 inhibitor; ≥1 GA was detected in 112 pts. Median age at time of ctDNA collection was 72 and median (range) number of GA per sample was 4 (0-80); 110 pts had ≥1 SNV & 39 pts ≥1 CNV. Presence of RAF1 and BRCA1 GA correlated with shorter OS (p=0.007; p=0.070, respectively). Serial samples showed new and resolution of some GA.

ctDNA GA were detected in most pts with metastatic UC and appeared comparable to those from prior tumor tissue NGS studies. BRCA1 GA correlated with poor outcome suggesting that synthetic lethality with PARP inhibitors may be clinically useful and tested in clinical trials. Serial sample analysis revealed genomic evolution.

Presented by: Petros Grivas, MD, Department of Medicine, Division of Oncology, University of Washington and Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance, Seattle, WA

Written by: Stephen B. Williams, M.D., Associate Professor, Division of Urology, The University of Texas Medical Branch, Galveston, TX. and Ashish M. Kamat, M.D. Professor, Department of Urology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX at the 16th Annual Meeting of the International Bladder Cancer Network (IBCN) October 11-13, 2018 - the Inntel Hotels Rotterdam Centre, Rotterdam, The Netherlands
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