ASCO GU 2017: Evolution of circulating tumor DNA profile from 1st line to 2nd line therapy in metastatic renal cell carcinoma.

Orlando, Florida USA (UroToday.com) Multiple targeted therapies are approved for mRCC. In order to improve treatment choices, efforts such as TCGA have revealed insights into tumor biology. One must remember that most such efforts represent earlier stage patients and they did not implement any predictive biomarker. Circulating biomarkers represent a practical means os serially assessing tumor biology. It is known that advanced tumors shed DNA in blood and that ctDNA can account for tumor heterogeneity.

The aim of the present trial was to determine the landscape of advanced RCC using ctDNA and to assess changes across patients receiving 1st and subsequent lines of therapy. Patients had advanced RCC and consented to ctDNA assessment as part of routine clinical care. CtDNA was measured with the Guardant360 assay. First line treatment was defined as treatment with sunitinib, pazopanib,bevacizumab and temsirolimus. All other drugs were considered post 1st line. CtDNA was collected from 224 patients. 71% had clear cell RCC and 11% papillary RCC. ctDNA was found in 79% of patients. An average of 3.3 genomic alteration (GA) were detected per patient. 89% of all mutations were single nucleotide variants and small insertions/deletion. The most common alterations were in TP53 and VHL genes. The frequency of these alterations was much higher in the post 1st line cohort.

Finally, P53 and VHL alterations were more common in this trial compared with TCGA date. All these alterations underscore potential mechanisms of resistance to treatment.

First Author: Sumantha Pal, MD, City of Hope, USA

Written By: Miki Haifler, MD, M.Sc, Fox Chase Cancer Center

at the 2017 Genitourinary Cancers Symposium - February 16 - 18, 2017 – Orlando, Florida USA

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