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ORAL 38 - Liquid Biopsies (ID 147)
- Event: WCLC 2015
- Type: Oral Session
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
ORAL38.02 - Biopsy-Free Circulating Tumor DNA Assay Identifies Actionable Mutations in Lung Cancer (ID 2163)
16:45 - 18:15 | Author(s): V. Villaflor
The National Comprehensive Cancer Network (NCCN) non-small cell lung cancer guidelines recommend testing for seven genomic targets amenable to matched therapies, including point mutations and insertions/deletions (indels) in EGFR and ERBB2 (HER2), point mutations in BRAF, fusions in ALK, RET and ROS1, and amplification of the MET gene. Novel digital sequencing technology allows assessment of these biomarkers without an invasive tissue biopsy.
We prospectively tested cell free DNA from 43 advanced non-small cell lung cancer patients using a cell-free circulating tumor DNA (ctDNA) next-generation sequencing (NGS) panel of 54 cancer genes (Guardant360). Single nucleotide variants (SNVs) in 54 genes and copy number variants (CNVs) in 3 genes (EGFR, ERBB2 and MET) were reported quantitatively as the mutant allele fraction (MAF) in cell-free DNA and the absolute copy numbers in plasma, respectively.
79% of patients had at least one ctDNA alteration detected. Five (11.6%) had sensitizing mutations in EGFR: EGFR L858R (n=1), EGFR exon 19 deletions (n=4), which may respond to first line tyrosine kinase inhibitors (TKIs) such as erlotinib and afatinib. Three patients with EGFR exon 19 deletions had concurrent T790M resistance mutations, which develop in over half of patients on early generation TKIs. MET amplification, which may respond to crizotinib, was identified in one patient. Clinical outcomes will be reported at the time of presentation. Of the 43 patients in our series, actionable findings were identified in 35 patients (81.4%), with an approved therapy in 5 (11.4%), off label therapies in 19 (44.2%), and clinical trials in 28 (65.1%).
In our series of NSCLC patients with advanced disease, digital sequencing of cell-free circulating tumor DNA yielded results in approximately 80% of patients. Of these, over 80% had an actionable alteration, including 5 cases with EGFR alterations that could benefit from an approved therapy. Biopsy-free comprehensive sequencing of a patient’s cancer can empower informed treatment decisions from a simple blood draw, especially when repeat tissue biopsy is not feasible or tissue NGS is uninformative.
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