Monitoring EGFR-T790M mutation in serum/plasma for prediction of response to third-generation EGFR inhibitors in patients with lung cancer
Year: 2018
Type: article
Study design: Observational Study
Abstract: // Teresa Morán 1 , Eudald Felip 1 , Joaquim Bosch-Barrera 2 , Itziar de Aguirre 3 , Jose Luis Ramirez 3 , Carles Mesia 4 , Enric Carcereny 1 , Diana Roa 2 , Elia Sais 2 , Yolanda García 5 , Remei Blanco 6 , Silvia Sanchez 7 , Claudia Rosa Villacorta 7 , Cristina Queralt 3 , Jose María Velarde 8 and Rafael Rosell 3 1 Medical Oncology Department, Catalan Institute of Oncology - Badalona, Hospital Universitari Germans Trias i Pujol, Badalona, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain 2 Medical Oncology Department, Catalan Institute of Oncology-Girona, Hospital Universitari Doctor Trueta Girona, Girona, Spain 3 Molecular Biology Laboratory of Cancer Dr. Rosell, Can Ruti Campus: Institute Germans Trias i Pujol (IGTP), Catalan Institute of Oncology, Badalona, Spain 4 Medical Oncology Department, Catalan Institute of Oncology - Hospital Duran i Reynalds, l’Hospitalet de Llobregat, Barcelona, Spain 5 Medical Oncology Department, Hospital Parc Taulí, Sabadell, Barcelona, Spain 6 Medical Oncology Department, Consorci Sanitari de Terrassa, Terrassa, Barcelona, Spain 7 Research Nurse Team, Catalan Institute of Oncology - Badalona, Hospital Universitari Germans Trias i Pujol, Badalona, Spain 8 Statistics Department, Fundació Germans Trias i Pujol, Badalona, Spain Correspondence to: Teresa Morán, email: [email protected] Keywords: EGFR-T790M mutation; serum/plasma; osimertinib; acquired resistance; EGFR tyrosine kinase inhibitors Received: March 19, 2018 Accepted: May 02, 2018 Published: June 05, 2018 ABSTRACT Background: Osimertinib is efficacious in lung cancer patients with epidermal growth factor receptor ( EGFR ) mutations and acquired resistance (AR) to EGFR tyrosine kinase inhibitors due to EGFR -T790M mutation (T790M). We sought to describe T790M changes in serum/plasma during osimertinib therapy and correlate these changes with treatment outcomes. Material and methods: Serum/plasma from EGFR -mutant lung cancer patients with T790M-AR was collected before and during osimertinib treatment. Changes in T790M were evaluated using a peptide-nucleic acid-PCR assay, and correlated with clinical and radiographic response. Results: Thirteen patients were included. Median time on osimertinib treatment was 10.6 months with a median progression-free survival of 13.6 months. Best response to osimertinib was partial response (PR), stable disease (SD) or progression (PD) in 46.1%, 30.8% and 23.1% of patients, respectively. Most of the patients were paucisymptomatic at baseline. Symptom improvement was reported in 66.6% of responder patients; while symptoms remained stable in 75% of patients with SD, and 66% of patients with PD had clinical deterioration. Three patterns of T790M changes during osimertinib treatment were identified. T790 remained detectable with PD or a short-lasting SD in 15.4% of the patients. T790M disappeared in 69.2% of patients with PR or SD. T790M disappeared, despite clinical and/or radiographic progression in 15.4% of the patients. Conclusion: Changes of T790M in serum/plasma in EGFR -mutant lung cancer patients with T790M-AR might be a useful marker of symptomatic and radiographic outcome to osimertinib. Longer follow-up is needed to establish if subsequent emergence of T790M could be a marker of resistance.
Source: Oncotarget
Institutions: Universitat Autònoma de Barcelona, Institut Català d'Oncologia, Hospital Universitari Germans Trias i Pujol, Hospital Universitari de Girona Doctor Josep Trueta, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Duran i Reynals Hospital, Corporació Sanitària Parc Taulí, Consorci Sanitari de Terrassa
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W2807660816