8P - EGFR, KRAS, BRAF, and PI3K mutations and ALK rearrangement in 327 consecutive Spanish non-squamous NSCLC patients

Date 15 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session Poster lunch
Topics Lung and other Thoracic Tumours
Pathology/Molecular Biology
Translational Research
Presenter Paloma Martin Martorell
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors P. Martin Martorell1, M. Huerta2, A. Compañ Quilis3, M. Abellán4, S. Blesa4, F. Chaves4, D. Dualde Beltrán5, A. Fernández Do Nascimento2, A. Insa2
  • 1Hematology And Medical Oncology, Hospital Clinico Universitario de Valencia, 46010 - Valencia/ES
  • 2Hematology And Medical Oncology, Hospital Clinico Universitario de Valencia, Valencia/ES
  • 3Pathology, Hospital Clinico Universitario de Valencia, Valencia/ES
  • 4Genotyping And Genetic Diagnosis Unit, Hospital Clinico Universitario de Valencia, Valencia/ES
  • 5Radiation Oncology, Hospital Clinico Universitario de Valencia, Valencia/ES

Abstract

Background

Although it was initially thought many driver alterations were mutually exclusive, it might not be so. These pathways may interact in a dynamic way. Whether these mutations are present in different cellular clones that emerge as a result of treatment pressure or they co-exist in the same cell is not yet fully clear.

Methods

Between Nov. 2011Aug. 2014 clinical data from consecutive newly diagnosed lung cancer patients in our center were prospectively collected in a database. Mutational analysis of EGFR, KRAS, BRAF and PI3K as well as ALK rearrangement was determined in all metastatic Nsq-NSCLC. EGFR mutational analysis was carried out using next generation sequencing using the Cobas and Junior diagnostic method. KRAS, BRAF and Pi3Kanalysis was determined by next generation sequencing using Sequencing Multiplex and Junior System. ALK rearrangement was carried out by FISH and confirmed by IHQ (D5F3, Ventana diagnostics).

Results

327 patients were diagnosed with Nsq-NSCLC. 216 (66%) of the 327 patients had EGFR analysed, 132 (40.3%) KRAS, 128 (39.1%) BRAF, 122 (37.3%) PI3K and 126 (38.5%) ALK. Of the 216 with EGFR determination, 58 (26.8%) harbored EGFR mutations. Exon 19 deletions (44.4%), exon 21 mutations (L858R and L861Q – 47.2%), exon 18 mutations G719A/C/S (13.8%). Fifty four (40.9%) KRAS mutations, 4 (3.1%) BRAF mutations, 12 (9.8%) PI3K mutations and 8 (6.3%) ALK re-arranged.14 had co-existent mutations: 2 EGFR/ALK re-arrangements, 9 EGFR/KRAS, 4 EGFR/PI3K, and 2 EGFR/BRAF. 3 patients had triple mutations in EGFR/BRAF/ALK, and 2 in EGFR/KRAS/PI3K.

Conclusions

We show that these mutations may co-exist previous to receiving targeted therapy. Whether they represent a primary or acquired resistance to targeted therapy is important to determine (data to be presented on the tissue origin – primary tumor vs metastasis). In our series, 78.5% of the patients were heavy smokers. Most patients were not exposed to targeted therapy, but of those who were, most did not respond.

Clinical trial identification


Legal entity responsible for the study

Hospital Clínico Universitario

Funding

Research Foundation of Hospital Clínico Universitario de Valencia (Spain)-INCLIVA

Disclosure

All authors have declared no conflicts of interest.