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Association ofEGFRL858R Mutation in Circulating Free DNA With Survival in the EURTAC Trial

作者:Niki Karachaliou, Clara Mayo de las Casas, Cristina Queralt, Itziar de Aguirre, B. Melloni, Felipe Cardenal, Ramón García-Gómez, Bartomeu Massutí, José Miguel Sánchez, Ruth Porta, Santiago Ponce-Aix, Teresa Morán, Enric Carcereny, Enriqueta Felip, Isabel Bover, Amelia Insa, Noemı́ Reguart, Dolores Isla, Alain Vergnenégre, Filippo de Marinis, Radj Gervais, R. Corre, Luis G Paz-Ares, Daniela Morales-Espinosa, Santiago Viteri, Ana Drozdowskyj, Núria Jordana‐Ariza, Jose Luis Ramirez-Serrano, Miguel Ángel Molina‐Vila, Rafael Rosell · 发表于:JAMA Oncology · 年份:2015 · DOI:10.1001/jamaoncol.2014.257 · 被引用次数:240 · 研究领域:Lung Cancer Treatments and Mutations、Cancer Genomics and Diagnostics、Lung Cancer Research Studies

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 ...