1309P - ERMETIC-2 project : Impact of systematic EGFR and KRAS mutation evaluation by alternative testing methods on progression-free (PFS) and overall sur...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Personalised Medicine
Translational Research
Presenter Michele Beau-Faller
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors M. Beau-Faller1, M. Texier2, H. Blons3, N. Richard4, F. Escande5, I. Bièche6, S. Lizard7, F. De Fraipont8, F. Morin9, G. Zalcman10, J. Pignon11, J. Cadranel12
  • 1Laboratoire De Biochimie Et De Biologie Moléculaire 1, Av. Molière 67098 Strasbourg Cedex Tel : +33 3 88 12 71 79 E/m Laboratoire De Biochimie Et De Biologie Moléculaire, Hôpitaux Universitaires de Strasbourg et INSERM U682 Hôpital de Hautepierre, 67098 - strasbourg/FR
  • 2Biostatistics, Gustave Roussy, 94805 - Villejuif Cedex/FR
  • 3Umr-s775, Université Paris Descartes, Paris/FR
  • 4Laboratoire De Génétique Moléculaire, CHU, Caen/FR
  • 5Pôle De Biologie Pathologie Génétique, CHRU, LILLE/FR
  • 6Laboratoire D'oncogénétique, Institut Curie, PARIS/FR
  • 7Unité De Biologie Moléculaire, CEntre Georges François Leclerc, DIJON/FR
  • 8Laboratoire De Génétique, CHU, Grenoble/FR
  • 9-, IFCT (Intergroupe Francophone de Cancérologie Thoracique)., 75009 - PARIS/FR
  • 10Service De Pneumologie, C.H.U. de Caen, FR-14033 - Caen CEDEX /FR
  • 11Biostatistics, Gustave Roussy, 94805 - Villejuif/FR
  • 12Service De Pneumologie, APHP, CancerEst, Tenon University Hospital, PARIS/FR

Abstract

Aim

ERMETIC is a French (IFCT) prospective study of EGFR and KRAS mutation evaluation by sequencing in patients with advanced NSCLC treated by E. The aim of the ERMETIC-2 project was to determine the prognostic impact of using alternative molecular techniques in the available tumor samples of the ERMETIC cohort.

Methods

239 patients (pts) with tumors were available for re-analyze by previously described alternative techniques (J Mol Diag 2014). Multivariate Cox model with performance status, histology, smoking status and initial number of metastatic sites was used for prognostic analysis.

Results

Population included 59% of adenocarcinoma, 37% of women and 19% of non-smokers. Overall mutation rate is 46%: 31 EGFR mutations (13%) and 78 KRAS mutations (33%); 40 new mutations compared to previous study were found: 9 EGFR and 31 KRAS. In the ERMETIC 2 cohort, OS and PFS remained significantly (global test p < 0.01) better for EGFR mutated (hazard ration [HR] 0.57 [95%CI: 0.33-1.00] and 0.47 [0.28-0.78] respectively) and worse for KRAS mutated (HR 1.35 [0.97-1.88] and 1.16 respectively [0.85-1.59]) compared to wild-type (WT) NSCLC. No prognostic significant difference was found in the 177 pts common to both cohorts between pts with KRAS mutation in both cohorts (n= 28) and those with new (n = 31) mutations. In the 228 pts with several techniques, KRAS mutations detected by less sensitive technique (n = 42) have a lower OS compared to WT than those detected only by the best sensitive technique (n = 34), but are not significantly different: 1.63 (1.09-2.44) and 1.08 (0.69-1.69); results between techniques were similar for PFS. Among the KRAS mutated group, no prognostic difference was found comparing mutations in codon 12 (67 pts) and 13 (8 pts), or transitions (24 pts) and transversions (51 pts).

Conclusions

1. KRAS but not EGFR mutations were detected in higher proportion by alternative molecular techniques compared to sequencing. 2. KRAS mutations identified by more sensitive technique did not identified a group of patients with a different prognostic.

Disclosure

All authors have declared no conflicts of interest.