Genomic Alterations in Metastatic Renal Cell Carcinoma

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Patients with metastatic renal carcinoma treated with post-frontline agents had increased genomic alterations.
Patients with metastatic renal carcinoma treated with post-frontline agents had increased genomic alterations.

ORLANDO, FL Patients with metastatic renal carcinoma (mRCC) treated with post-frontline agents had increased genomic alterations in TP53, NF1, EGFR, and PIK3CA, according to a study presented at the 2017 Genitourinary Cancers Symposium.1 

"There are multiple targeted therapies approved for mRCC, including VEGF-directed therapies, mTOR inhibitors, and checkpoint inhibitors," said Sumanta K. Pal, MD, urologic oncologist at City of Hope, Duarte, California. "While efforts such as the TCGA have shed some light on the tumor biology, it is important to keep in mind that these datasets reflect earlier stages of disease. Certainly, there may be an evolution of tumor biology as patients progress toward metastasis."

Because circulating biomarkers represent a practical means of assessing tumor biology in real time, with circulating tumor DNA potentially accounting for tumor heterogeneity, Dr Pal and colleagues investigated temporal changes in genomic profiles of patients with mRCC by evaluating circulating tumor DNA.

The researchers obtained data from 244 patients who received circulating tumor DNA profiling as part of routine clinical care at progression using Guardant360, a CLIA-certified comprehensive plasma assay. Of those, 64 and 56 patients were coded as receiving frontline and post-first-line agents, respectively.

The investigators detected genomic alterations in 78.6% of patients, with the most common genomic alterations being TP53, VHL, EGFR, NF1, and ARID1A in the overall cohort.

"Of the 633 genomic alterations identified, the preponderance of single nucleotide variants and small insertions/deletions represented 89% of all mutation," Dr Pal added. "The average number of genomic alterations detected per patients was 3.3."

Among the patients receiving first-line therapy, the average number of circulating tumor DNA alterations was 2.9 compared with 3.7 in those receiving second-line therapy.

RELATED: Impact of Early Immunotherapy Discontinuation in mRCC

"Compared to patients receiving first-line therapy, patients receiving post-first-line agents had increased genomic alterations in TP53, NF1, EGFR, and PIK3CA," said Dr Pal. "These alterations underscore potential mechanisms of resistance."

Investigators of the study are working to add detailed data on demographics and clinical outcomes to the current dataset.

Reference

  1. Pal SK, Sonpavde G, Agarwal N, et al. Evolution of circulating tumor DNA (ctDNA) profile from first-line (1L) to second-line (2L) therapy in metastatic renal cell carcinoma (mRCC). Paper presented at: 2017 Genitourinary Cancers Symposium; February 16-18, 2017; Orlando, FL.

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