Monitoring EGFR-T790M mutation in serum/plasma for prediction of response to third-generation EGFR inhibitors in patients with lung cancer
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Teresa Morán1, Eudald Felip1, Joaquim Bosch-Barrera2, Itziar de Aguirre3, Jose Luis Ramirez3, Carles Mesia4, Enric Carcereny1, Diana Roa2, Elia Sais2, Yolanda García5, Remei Blanco6, Silvia Sanchez7, Claudia Rosa Villacorta7, Cristina Queralt3, Jose María Velarde8 and Rafael Rosell3
1Medical Oncology Department, Catalan Institute of Oncology - Badalona, Hospital Universitari Germans Trias i Pujol, Badalona, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
2Medical Oncology Department, Catalan Institute of Oncology-Girona, Hospital Universitari Doctor Trueta Girona, Girona, Spain
3Molecular Biology Laboratory of Cancer Dr. Rosell, Can Ruti Campus: Institute Germans Trias i Pujol (IGTP), Catalan Institute of Oncology, Badalona, Spain
4Medical Oncology Department, Catalan Institute of Oncology - Hospital Duran i Reynalds, l’Hospitalet de Llobregat, Barcelona, Spain
5Medical Oncology Department, Hospital Parc Taulí, Sabadell, Barcelona, Spain
6Medical Oncology Department, Consorci Sanitari de Terrassa, Terrassa, Barcelona, Spain
7Research Nurse Team, Catalan Institute of Oncology - Badalona, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
8Statistics Department, Fundació Germans Trias i Pujol, Badalona, Spain
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
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.
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