148P - Concordance between detection of EGFR mutations on tissue and in circulating free tumor DNA (cftDNA) in newly diagnosed metastatic lung adenocarcin...

Date 15 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session Poster lunch
Topics Translational Research
Non-Small Cell Lung Cancer
Basic Principles in the Management and Treatment (of cancer)
Presenter Antonello Veccia
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors A. Veccia1, O. Caffo2, S. Girlando3, S. Fasanella3, M. Dipasquale2, V. Murgia2, M. Barbareschi4, E. Galligioni2
  • 1Medical Oncology, Ospedale Sta Chiara, 38122 - Trento/IT
  • 2Medical Oncology, Ospedale Sta Chiara, Trento/IT
  • 3Molecular Biology, Ospedale Sta Chiara, Trento/IT
  • 4Pathological Anatomy, Ospedale Sta Chiara, Trento/IT

Abstract

Background

The detection of EGFR mutations may predict sensitivity to EGFR-TKIs (Tyrosine Kinases Inhibitors) in mLA. However, small biopsies or cytological samples often provide limited or insufficient tumor tissue for molecular analysis. Moreover, a re-biopsy is not always technically feasible to identify emerging mechanisms of resistance at disease progression. Therefore, cftDNA represents an alternative source of DNA for genotyping the tumor.

Methods

Patients (pts) with newly diagnosed mLA were included in the study and treated with EGFR-TKIs or chemotherapy as first-line treatment according to the EGFR mutational status. EGFR and K-ras mutations were detected on tumor tissue by Pyrosequencing (Pyr) or Sequenom MassArray (SMA) before starting treatment; N-ras, B-Raf, DDR2 and PK3CA mutations were identified by SMA, too. Only EGFR mutations were found on cftDNA by a Real Time PCR (RT PCR) before starting therapy, during the treatment and at disease progression. The degree of concordance between EGFR mutational analysis on tissue and in blood was evaluated.

Results

Between April and November 2015, analysis of tumor tissue was performed in 17 pts (M/F = 8/9) with a median age of 65 years, while it was not possible in 3 cases due to insufficient material. EGFR mutations were detected in 9/17 patients: 6 cases of exon 19 deletions (five E746-A750 del, one E747-T751 del) and 3 cases of exon 21 substitution (L858R). All mutated pts, whose high percentage (53%) was due to selection bias of the study, received gefitinib or erlotinib as first line treatment; wild type pts underwent platinum-based chemotherapy. Analysis of EGFR mutations on cftDNA showed a 100% concordance with tissue detection. Moreover, pts with poor histological tissue appeared wild type on cftDNA analysis.

Conclusions

RT PCR confirmed to be a valid method to detect EGFR mutations in blood, in particular when histological tissue is insufficient to molecular analysis and a re-biopsy is difficult to perform. It showed a 100% concordance with tissue analysis methods. Moreover, cftDNA better mirrors the heterogeneity of mLA and could be useful to monitor disease during the treatment.

Clinical trial identification

The study has not a protocol number.

The procedures were performed according to the clinical practice and to the rules of local ethical commitee.

Legal entity responsible for the study

Azienda Provinciale per i Servizi Sanitari di Trento, whose Santa Chiara Hospital is part.

Funding

The study was not funded by foundation or academic group. The Azienda Provinciale per i Servizi Sanitari di Trento, of which Santa Chiara Hospital is part, proceeded itself to the study self-financing.

Disclosure

O. Caffo: Honoraria from Sanofi Aventis, Astellas and Janssen. All other authors have declared no conflicts of interest.