EGFR L858R Mutation Linked to Short NSCLC Overall Survival

Advanced non-small-cell lung cancer prognosis differs with epidermal growth factor receptor mutation type

medwireNews: EURTAC trial results confirm the existence of multiple clinical phenotypes of epidermal growth factor receptor (EGFR) mutations in patients with advanced non-small-cell lung cancer (NSCLC).

The EURTAC (European Tarceva vs Chemotherapy) researchers used a peptide nucleic acid-mediated 5′ nuclease real-time polymerase chain reaction (TaqMan) assay to examine for EGFR mutations in circulating free (cf)DNA from 97 patients with tumour tissue-confirmed EGFR mutations and adequate blood samples .

The “liquid biopsy” identified EGFR mutations in 78% of these cases, including 47 patients with the exon 19 deletion and 29 with the L858R mutation, explain Rafael Rosell, from Hospital Germans Trias i Pujol in Badalona, Spain, and co-authors in JAMA Oncology.

Patients given the tyrosine kinase inhibitor erlotinib had a trend towards longer overall survival than those given chemotherapy, regardless of their EGFR mutation status.

But regardless of treatment received, patients with a cfDNA-detected L858R mutation had significantly shorter median overall survival (OS) than those with the exon 19 deletion, at 13.7 and 30.0 months, respectively. This was also true for patients with a L858R mutation detected in tumour samples only, at 17.7 months versus 24.9 months for a tissue-identified exon 19 deletion.

In addition, among the 40 erlotinib-treated patients with cfDNA-detected mutations, median OS was also significantly shorter among the L858R carriers than exon 19 deletion carriers, at 13.7 versus 34.4 months.

Univariate analysis confirmed that a tissue- or cfDNA-detected L858R mutation was associated with shorter OS with hazard ratios (HRs) of 1.85 and 2.80, respectively.

Finally, initial analysis indicated that a cfDNA-detected L858R mutation was associated with shorter progression-free survival but in multivariate analysis erlotinib treatment was the only significant predictor of this outcome, with an HR of 0.41.

“The shorter OS—both for all patients and for those receiving erlotinib therapy—observed in the present study among patients with L858R mutations in tissue or cfDNA reinforces this concept of the existence of more than 1 clinical phenotype of EGFR-mutant NSCLC and suggests that in future analyses, outcomes of patients with exon 19 deletions and those with L858R mutations should not be pooled”, Rafael Rosell et al write.

“The exon-specific activity of EGFR [tyrosine kinase inhibitors] warrants further exploration.”


Karachaliou N, Mayo-de las Casas C, Queralt C, et al. Association of EGFR L858R mutation in circulating free DNA with survival in the EURTAC trial. JAMA Oncol 2015; Advance online publication 26 February. doi:10.1001/jamaoncol.2014.257

medwireNews ( ) is an independent clinical news service provided by Springer Healthcare Limited.© Springer Healthcare Ltd; 2015