ctDNA Concordant with Tissue Genomic Analysis in RCC – Cancer Therapy Advisor

Genomic analysis using circulating cell-free tumor DNA (ctDNA) was highly concordant with, and complementary to, tissue genomic analysis among patients with advanced renal cell carcinoma (mRCC), according to results of a retrospective study presented at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.

Exclusive GAs [genomic alterations] found on both platforms suggests tumor evolution over time and treatment, which may assist in guiding treatment selection in mRCC, Zeynep Zengin, MD, of City of Hope Comprehensive Cancer Center in Duarte, California, and presenter of the study, said.

The single-center, retrospective studied analyzed data from 847consecutive patients with stage IIIB to IV RCC who underwent ctDNA testing using the Guardant360 next-generation sequencing (NGS) assay. Serial assessment of ctDNA was performed on a subset of 39 patients. GAs detected by ctDNA NGS were compared with GAs detected by NGS or whole-exome sequencing of tissue DNA with commercially available platforms (Foundation Medicine and Ashion Analytics, respectively). The median time between the ctDNA and tissue testing was 15.3 months.

Among the ctDNA samples, 72% harbored 1 or more GA, with the most frequent genes affected including TP53 at 37%, VHL at 22%, and EGFR at 6%.

Alterations along the mTOR pathway were also well represented, including PTEN, PIK3CA, and NF1, Dr Zengin said. She noted that approximately 6% of patients harbored mutations in DNA repair genes, such as BRCA1, BRCA2, ATM, and CDK12.

Serial analysis of ctDNA demonstrated that the frequency of GAs in EGFR and PTEN increased over time.

Among the tissue DNA samples, the most frequent genes with GAs was VHL at 63.8%, PMBRM1 at 44.7%, and SETD2 at 39.1%. Both PMBRM1 and SETD2 were not evaluated by the ctDNA assay.

A total of 154 GAs were detected across both ctDNA and tissue DNA assay, when including only the genes assessed by the ctDNA assay. Of these GAs, 17.4% were identified by both tests, whereas 38.8% were detected only in blood and 43.8% were detected only in tissue.

The overlap increased when samples were stratified by the amount of time between their collections. When samples were collected within 6 months of each other, the overlap was 39.3%, whereas samples collected more than 6 months apart had an overlap of 10.8%.

The concordance was high between the tests, with a cumulative rate of 96.2%.

Dr Zengin concluded that concordance analysis suggests that ctDNA and tissue-based genomic profiling are complementary.

Disclosures: Multiple authors declared affiliations with industry. Please refer to the original abstract for a full list of disclosures.

Read more of Cancer Therapy Advisors coverage of the ESMO Virtual Congress 2020 by visiting the conference page.

Reference

Zengin ZB, Weipert C, Hsu J, et al. Assessment of circulating cell-free tumor DNA (ctDNA) in 847 patients (pts) with metastatic renal cell carcinoma (mRCC) and concordance with tissue-based testing. Presented at: European Society for Medical Oncology (ESMO) Virtual Congress 2020; September 19-21, 2020. Abstract 701O.

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ctDNA Concordant with Tissue Genomic Analysis in RCC - Cancer Therapy Advisor