Liquid Biopsies Are Highly Sensitive for Actionable Mutations in Solid Tumors

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Alterations conferring resistance to targeted agents were identified among 18% of samples from NSCLC, breast, colorectal, and prostate cancers, melanoma, and gastrointestinal stromal tumors.
Alterations conferring resistance to targeted agents were identified among 18% of samples from NSCLC, breast, colorectal, and prostate cancers, melanoma, and gastrointestinal stromal tumors.
The following article features coverage from the European Society of Medical Oncology (ESMO) 2017 Congress in Madrid, Spain. Click here to read more of Cancer Therapy Advisor's conference coverage.

Next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) is highly sensitive for detecting clinically actionable mutations among patients with advanced solid tumors, according to a study presented at the European Society for Medical Oncology (ESMO) 2017 Congress in Spain.1

The use of ctDNA, or liquid biopsy, for noninvasive molecular tumor profiling has been increasing, though few large datasets on the clinical use of liquid biopsies are published. The purpose of this study was to evaluate the clinical implications of NGS of ctDNA among patients with advanced solid tumors.

The study analyzed the somatic genomic profiles of 35,492 plasma samples from 30,024 patients with advanced solid tumors. The analysis included up to 73 genes using NGS. The tumor types included in the cohort were non–small cell lung cancer (NSCLC; 39%), breast cancer (16%), colorectal cancer (10%), and other solid cancer types (35%).

The study found ctDNA alterations in 86% (range, 82% to 88%) of the samples and 19% of patients had at least 1 alteration associated with a targeted agent approved by the US Food and Drug Administration.

Alterations conferring resistance to targeted agents were identified among 18% of samples from NSCLC, breast, colorectal, and prostate cancers, melanoma, and gastrointestinal stromal tumors.

Compared with 646 samples with matched tissue tests, the positive predictive value (PPV) was over 90% for clinically actionable mutations. The PPV was 92% to 100% for EGFR mutations, 92% for ALK/RET/ROS1 fusions, 95% for the BRAFV600E variant, 94% for KRAS mutations, and 100% for MET E14 skipping mutations.

According to the investigators, this liquid biopsy dataset “highlights the clinical impact of identifying alterations that are targetable by drugs with regulatory approval, including emergent resistance alterations.”

RELATED: Liquid Biopsies for Circulating Tumor Cells: A New Prognostic Tool?

Read more of Cancer Therapy Advisor's coverage of the European Society of Medical Oncology (ESMO) 2017 Congress by visiting the conference page.

Reference

  1. Pal SK, Brooks C, Chudova D, et al. Clinical implications of genomic variants identified in over 30,000 advanced-stage cancer patients by next-generation sequencing of circulating tumor DNA. Presented at: 2017 ESMO Congress; Madrid, Spain: September 8-12, 2017. Abstract 1702O.

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