Liquid Biopsy Urine Test Detects Mutations In Lung Cancer

While lung cancer is one of the most aggressive malignancies, progress has been made in the advancement of therapeutic strategies against the disease and in particular, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs).

In non–small cell lung cancer (NSCLC) patients with EGFR mutations, clinical response rates have demonstrated as high as 80%, after about six to 12 months, most tumors develop acquired resistance to these targeted therapies. Such resistance has identified the secondary T790M mutation, which occurs in approximately 60% of patients with acquired resistance to EGFR-TKIs and is reported to negate the benefits of treatment.


Scientists at Stanford University Medical Center (CA, USA) and their colleagues compared EGFR mutation detection in circulating tumor DNA from blood and urine to that in matched tissue in TIGER-X (NCT01526928), a phase 1/2 study of rociletinib in patients with mutant EGFR positive advanced NSCLC.

EGFR status was assessed by the therascreen EGFR test (Qiagen, Hilden, Germany) in tissue, BEAMing Digital PCR technology (Sysmex, Kobe, Japan) in plasma, and a quantitative short footprint assay method that uses next-generation sequencing (Trovagene, San Diego, Ca, USA) in urine. Of 417 patients in two dosing groups, 331 of 417 were T790M+ by central tissue genotyping; 189 of 242 were T790M+ by plasma genotyping; and 136 of 169 were T790M+ by urine genotyping. Confirmed investigator-assessed objective response rate (ORR) and median duration of response (mDOR) were similar regardless of sample type.

Four of 14 pts who were T790M+ in plasma but T790M− in tissue responded; three of seven patients who were T790M+ in urine but T790M− in tissue responded. Shrinkage of target lesions correlated with higher T790M: activating mutation ratio in plasma. With tissue as reference, positive percent agreement for T790M status between matched plasma and tissue was 81.5% and 83.8% between matched urine and tissue. In both dosing groups, the most common treatment-related adverse events were hyperglycemia, diarrhea, nausea, and fatigue.

The authors concluded that in T790M+ pts, response was similar whether T790M status was identified by tissue, plasma or urine. Plasma and urine testing identified T790M mutations missed by biopsy due to tumor heterogeneity or inadequate sample quality. These data suggest plasma and urine EGFR analyses complement tissue biopsies in EGFR TKI resistant NSCLC.

Karen Reckamp, MD, a key study investigator, said, “Trovagene's urinary ctDNA test was able to identify the EGFR resistance mutation in cases not detected in tissue. The data suggest that urinary and plasma EGFR analyses complement tissue biopsies in EGFR tyrosine kinase inhibitor (TKI) resistant NSCLC.” The study was presented at the American Society of Clinical Oncology (ASCO) Annual Meeting held June 3-7, 2016, in Chicago, IL, USA.

Related Links:
Stanford University Medical Center
Qiagen
Sysmex
Trovagene