Abstract 3964: Large scale noninvasive screening of EGFR mutations in advanced NSCLC patients: the Identify platform experience
Authors: Mayo de las Casas Clara de la Caridad , Jordana Ariza Nùria , Garzón Ibañez Mónica , Balada Bel Ariadna , Bertrán-Alamillo Jordi , Pérez Rosado Ana , Viteri Ramirez Santiago , Morales Espinosa Daniela , Monasterio Juan Carlos , Karachaliou Niki , Molina-Vila Miguel Ángel , Rosell Rafael 
Published: July 2016

Abstract
Background: Activating mutations in the epidermal growth factor receptor gene (EGFR) confer sensitivity to tyrosine kinase inhibitors (TKIs) in patients with advanced non-small-cell lung cancer (NSCLC). Starting in June 2012, a nationwide platform (the Identify Blood Platform) was implemented in Spain for large-scale screening of EGFR mutations at presentation in the peripheral blood of unselected, advanced NSCLC patients. The Platform was restricted to patients with no tumor biopsy available or those with insufficient tumor tissue for genetic analyses. In May 2015, the Platform was extended to analyze blood of EGFR-mutated patients progressing to TKIs.
Methods: Analysis of EGFR mutations was performed by a central laboratory using a sensitive multiplex TaqMan assay in the presence of a PNA clamp. Circulating free DNA (cfDNA) was isolated from both serum and plasma using an automatic extractor, and mutational analyses were performed in quadruplicates. Patients harbouring EGFR mutations were informed as eligible for TKI treatment.
Results: From June 2012 to November 2015, 765 NSCLC patients from 102 institutions in Spain were prospectively screened at presentation for EGFR mutations in peripheral blood. In five cases (0.7%), blood collected was insufficient for molecular analysis. Clinical characteristics of the remaining 760 evaluable patients were as follows: prevalence of male (58.55%), former smokers (48.16%) and adenocarcinoma (79.34%). Sensitizing mutations were found in 76 of 760 patients (10%) and were prevalent in females (61.84%), never smokers (59.21%) and adenocarcinomas (80.26%). Of the 76 EGFR-mutated patients at presentation, 48 (63.16%) were positive in both serum and plasma, 19 (25%) only in plasma, and nine (11.84%) in serum alone. Regarding the type of mutation, 50 (65.8%) had exon 19 deletions, the most common being 15 bp deletions; 25 (32.9%) had L858R substitution, while L861Q mutation was detected in one patient (1.3%). Additionally, the T790M resistance mutation in exon 20 was analyzed in 223 pretreatment samples and not detected in any (0%). Finally, blood of 84 patients progressing to TKI treatment with no biopsy available was screened and T790M detected in 28 patients (33.33%).
Conclusions: Our results demonstrate the feasibility of large-scale, nationwide screening of EGFR mutations in peripheral blood of NSCLC patients at presentation and after TKI progression. Mutational analysis in blood is useful to inform treatment decisions, particularly in patients with no biopsy available or after TKI progression
Citation Format: Clara de la Caridad Mayo de las Casas, Nùria Jordana Ariza, Mónica Garzón Ibañez, Ariadna Balada Bel, Jordi Bertrán-Alamillo, Ana Pérez Rosado, Santiago Viteri Ramirez, Daniela Morales Espinosa, Juan Carlos Monasterio, Niki Karachaliou, Miguel Ángel Molina-Vila, Rafael Rosell. Large scale noninvasive screening of EGFR mutations in advanced NSCLC patients: the Identify platform experience. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3964.