Association of EGFR L858R Mutation in Circulating Free DNA With Survival in the EURTAC Trial

Niki Karachaliou, Clara Mayo-de las Casas, Cristina Queralt, Itziar de Aguirre, Boris Melloni, Felipe Cardenal, Ramon Garcia-Gomez, Bartomeu Massuti, José Miguel Sánchez, Ruth Porta, Santiago Ponce-Aix, Teresa Moran, Enric Carcereny, Enriqueta Felip, Isabel Bover, Amelia Insa, Noemí Reguart, Dolores Isla, Alain Vergnenegre, Filippo de MarinisRadj Gervais, Romain Corre, Luis Paz-Ares, Daniela Morales-Espinosa, Santiago Viteri, Ana Drozdowskyj, Núria Jordana-Ariza, Jose L uis Ramirez-Serrano, Miguel A ngel Molina-Vila, Rafael Rosell

Research output: Contribution to journalArticle

Abstract

IMPORTANCE: The EURTAC trial demonstrated the greater efficacy of erlotinib compared with chemotherapy for the first-line treatment of European patients with advanced non-small-cell lung cancer (NSCLC) harboring oncogenic epidermal growth factor receptor (EGFR) mutations (exon 19 deletion or L858R mutation in exon 21) in tumor tissue.

OBJECTIVE: To assess the feasibility of using circulating free DNA (cfDNA) from blood samples as a surrogate for tumor biopsy for determining EGFR mutation status and to correlate EGFR mutations in cfDNA with outcome.

DESIGN, SETTING, AND PARTICIPANTS: This prespecified analysis was a secondary objective of the EURTAC trial using patients included in the EURTAC trial from 2007 to 2011 with available baseline serum or plasma samples. Patients had advanced NSCLC, oncogenic EGFR mutations in the tumor, and no prior chemotherapy for metastatic disease and were treated with erlotinib or chemotherapy. EGFR mutations were examined in cfDNA isolated from 97 baseline blood samples by our novel peptide nucleic acid-mediated 5´ nuclease real-time polymerase chain reaction (TaqMan) assay.

MAIN OUTCOMES AND MEASURES: Overall survival (OS), progression-free survival (PFS), and response to therapy were correlated with type of EGFR mutations in cfDNA.

RESULTS: In samples from 76 of 97 (78%) patients with usable blood samples, EGFR mutations in cfDNA were detected. Median OS was shorter in patients with the L858R mutation in cfDNA than in those with the exon 19 deletion (13.7 [95% CI, 7.1-17.7] vs 30.0 [95% CI, 19.3-37.7] months; P 

CONCLUSIONS AND RELEVANCE: The peptide nucleic acid-mediated 5´ nuclease real-time polymerase chain reaction (TaqMan) assay used in this study can be used to efficiently assess EGFR mutations in cfDNA. The L858R mutation in cfDNA may be a novel surrogate prognostic marker.

TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00446225.

Original languageEnglish
Pages (from-to)149-157
Number of pages9
JournalJAMA oncology
Volume1
Issue number2
DOIs
Publication statusPublished - May 1 2015

ASJC Scopus subject areas

  • Medicine(all)

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    Karachaliou, N., Mayo-de las Casas, C., Queralt, C., de Aguirre, I., Melloni, B., Cardenal, F., Garcia-Gomez, R., Massuti, B., Sánchez, J. M., Porta, R., Ponce-Aix, S., Moran, T., Carcereny, E., Felip, E., Bover, I., Insa, A., Reguart, N., Isla, D., Vergnenegre, A., ... Rosell, R. (2015). Association of EGFR L858R Mutation in Circulating Free DNA With Survival in the EURTAC Trial. JAMA oncology, 1(2), 149-157. https://doi.org/10.1001/jamaoncol.2014.257