1273P - T790M resistant mutation in plasma of acquired resistant EGFR mutated non small cell lung cancer (NSCLC) patients - the TARZO trial (NCT00503971)

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Biomarkers
Non-Small-Cell Lung Cancer, Metastatic
Presenter Noemi Reguart
Authors N. Reguart1, E. Nadal2, M.A. Molina3, E. Carcereny4, C. Queralt4, A. Insa Molla5, I. Aguirre6, M. Taron7, D. Isla Casado8, R. Rosell9
  • 2Medical Oncology, Hospital Duran i Reynals (ICO), Barcelona/ES
  • 3Laboratoy Of Biology Department, Pangaea Biotech, USP Dexeus University Institute, 08028 - Barcelona/ES
  • 4Medical Oncology Service, Hospital Germans Trias i Pujol (ICO), 08916 - Badalona/ES
  • 5Serv. Hematologia Y Oncologia Medica, Hospital Clinico Universitario de Valencia, ES-46010 - Valencia/ES
  • 6Medical Oncology, Hospital Germans Trias i Pujol, Barcelona/ES
  • 7Medical Oncology, Hospital Germans Trias i Pujol (ICO), Barcelona/ES
  • 8Oncology Service, Hospital Clínico Universitario Lozano Blesa, Zaragoza/ES
  • 9Medical Oncology Service, Hospital Germans Trias i Pujol (ICO)Oncology, 08916 - Badalona/ES



EGFR-mutant NSCLC patients (pts) ultimately overcome resistant to tyrosine kinase inhibitors (TKIs). Among resistant mechanisms secondary EGFR T790M is the most frequent and account 50% of tumors. Previous data suggest that tumors with acquired T790M at post-progression biopsy specimen may have a more favorable prognosis and indolent progression. However, tumor re-biopsies at progression sites are scare in NSCLC patients and blood samples are a non-invasive method that may help to identify resistant mechanisms.

Material and methods

Pts with advanced NSCLC harboring EGFR mutations (Exon 19 and 21) and acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) were eligible. All patients where included in a phase II trial (TARZO) and treated with erlotinib 150 mg PO daily plus oral vorinostat 400 mg QD on days 1–7 and 15–21 in a 28-day cycle. Blood samples were required at study entry. We aim to determine the feasibility and incidence of T790M resistant mutation from plasma DNA from patients by mutation from cell free circulating DNA from patients using a 5′nuclease PCR assay (TaqMan assay) with a FAM MGB-labeled probe for the wild-type and a VIC MGB-labeled probe for the mutant sequence in the presence of a protein nucleic acid (PNA) clamp, which was designed to inhibit the amplification of the wild-type allele (Pangaea Biotech SL patent).


Twenty-five pts were included in the trial. From those, nineteen plasma specimens were obtained and used for DNA extraction. Overall T790M resistant mutation was detected from plasma DNA in 36.8% of the samples (7/19). There were no differences according patient characteristics (gender/ECOG-PS, smoking habits, number of previous treatments) or type of sensitizing mutation in tissue (Exon 19, L858R) and the presence of T790M. Median time to progression (TTP) and survival (OS) for the entire cohort was 2.4 months (IC 95% 1.2-3.6) and 13.2 months (IC 95% 2.23-26.9 months). Median TTP and OS were 2.4 vs 1.8 (p 0.076) and 13.7 vs 3.7 (p 0.095) in patients without and with T790M respectively.


T790M mutation is a common feature of resistant acquired EGFR mutated NSCLC patients and can be detected using plasma DNA.


All authors have declared no conflicts of interest.