EGFR mutations in circulating tumour DNA

Abstract

EGFR-mutated non-small-cell lung cancer (NSCLC) responds well to EGFR tyrosine-kinase inhibitors such as erlotinib. Median progression-free survival (PFS) reported in the erlotinib group of the European Tarceva versus Chemotherapy (EURTAC) trial 1 Rosell R Carcereny E Gervais R et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012; 13: 239-246 Summary Full Text Full Text PDF PubMed Scopus (4347) Google Scholar was 9·7 months compared with 5·2 months in the standard chemotherapy group (hazard ratio [HR] 0·37, 95% CI 0·25–0·54; p<0·0001). The HR for progression in EURTAC was much the same as the pooled HR for progression of 0·23 (95% CI 0·19–0·27) reported in four randomised studies in Asian patients. 1 Rosell R Carcereny E Gervais R et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012; 13: 239-246 Summary Full Text Full Text PDF PubMed Scopus (4347) Google Scholar However, the disease-free time to progression was still less than 1 year in EURTAC, 1 Rosell R Carcereny E Gervais R et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012; 13: 239-246 Summary Full Text Full Text PDF PubMed Scopus (4347) Google Scholar and thus identification of mechanisms of acquired resistance, including to the EGFR T790M resistance mutation, is crucial. To this end, a second biopsy at the time of progression is becoming increasingly accepted. However, often only a small amount of tumour is obtained and, to circumvent the problem of access to tissue samples, studies have focused on circulating tumour DNA (ctDNA) in plasma or serum. ctDNA can be used as a liquid biopsy, allowing repeated blood samples to be taken and changes in mutation status to be tracked throughout a cancer treatment, paving the way for a potential use in following up of treatment response, gauging prognosis, or monitoring of recurrence. 2 Schwarzenbach H Hoon DS Pantel K Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer. 2011; 11: 426-437 Crossref PubMed Scopus (1971) Google Scholar