Analysis of Circulating Free DNA May Replace Tumor Biopsy for Detection of Non-Small-Cell Lung Cancer

Chemotherapy) trial. EURTAC demonstrated the efficacy of erlotinib (Tarceva) compared with standard chemotherapy for the first-line treatment of European patients with advanced NSCLC with oncogenic EGFR mutations (exon 19 deletion or L858R mutations in exon 21) in tumor tissue.

Erlotinib is an epidermal growth factor receptor (EGFR) inhibitor that specifically targets the EGFR tyrosine kinase, which is highly expressed and occasionally mutated in various forms of cancer. It binds in a reversible fashion to the adenosine triphosphate (ATP) binding site of the receptor. For the signal to be transmitted, two EGFR molecules need to come together to form a homodimer. These then use the molecule of ATP to trans-phosphorylate each other on tyrosine residues, which generates phosphotyrosine residues, recruiting the phosphotyrosine-binding proteins to EGFR to assemble protein complexes that transduce signal cascades to the nucleus or activate other cellular biochemical processes. By inhibiting the ATP, formation of phosphotyrosine residues in EGFR is not possible and the signal cascades are not initiated.

In the current study researchers associated with the Spanish Lung Cancer Group examined the feasibility of using circulating free DNA (cfDNA) from blood samples of patients with advanced non-small-cell lung cancer as a replacement for tumor biopsies. To this end they used a novel peptide nucleic acid (PNA)–mediated 5´ nuclease real-time polymerase chain reaction (PCR) (TaqMan) assay to examine EGFR mutations in cfDNA isolated from 97 baseline blood samples obtained from patients that had participated in the EURTAC trial.

Results revealed that cfDNA EGFR mutations were detected in 76 of 97 samples (78%) from the patients. Median overall survival was shorter in patients with the L858R mutation in cfDNA than in those with the exon 19 deletion (13.7 versus 30 months). For the 76 patients with EGFR mutations in cfDNA, only erlotinib treatment was an independent predictor of longer disease progression-free survival.

Senior author Dr. Rafael Rosell, professor of medical oncology at the Hospital Germans Trias I Pujol (Badalona, Spain) said, "Testing of tumor tissue remains the recommended method for detecting the presence of oncogenic EGFR mutations; however, the amount of tumor tissue obtained by biopsy is often insufficient, especially in advanced NSCLC, raising the question of whether cfDNA may be used as a surrogate liquid biopsy for the noninvasive assessment of EGFR mutations."

The study was published in the February 26, 2015, online edition of JAMA Oncology.

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