1213PD - A comprehensive analysis of potentially targetable genetic aberrations and clinical findings in 821 patients with squamous-cell NSCLC – a compariso...

Date 09 October 2016
Event ESMO 2016 Congress
Session NSCLC, metastatic
Topics Non-small-cell lung cancer
Presenter Sophia Koleczko
Citation Annals of Oncology (2016) 27 (6): 416-454. 10.1093/annonc/mdw383
Authors S. Koleczko1, C. Schäpers1, M. Scheffler1, M. Ihle2, A. Kostenko3, S. Michels1, R. Fischer1, L. Nogova1, V. Brandes1, D. Abdulla4, F. Ueckeroth2, M. Thurat1, R. Frank1, A. Eisert1, E. Bitter1, C. Wömpner1, L. Gogl1, S. Merkelbach-Bruse2, R. Büttner2, J. Wolf1
  • 1Lung Cancer Group Cologne, Center For Integrated Oncology, University Hospital Cologne, 50937 - Köln/DE
  • 2Institute Of Pathology, University Hospital Cologne, Köln/DE
  • 3Dep. I For Internal Medicine, Center For Integrated Oncology, University Hospital Cologne, 50937 - Köln/DE
  • 4Lung Cancer Group Cologne, Center For Integrated Oncology, University Hospital Cologne, Köln/DE

Abstract

Background

In contrast to the improvements which have been made in the treatment of adenocarcinoma NSCLC, squamous-cell NSCLC (SqCLC) remains a therapeutic challenge. While there are recent advantages with immunotherapy approaches, targeted therapy still lacks of evidence regarding the frequency of driver aberrations in advanced SqCLC. We set out this study in order to characterize a large-scale set of patients with SqCLC genetically and clinically and compared the findings to the early-stage The Cancer Genome Atlas (TCGA) LUSC cohort.

Methods

Tumor biopsies of 821 patients were analyzed within the Network Genomic Medicine (NGM) lung cancer using next-generation parallel sequencing (NGS). The panel used consisted of 102 amplicons and 14 genes: KRAS, PIK3CA, BRAF, EGFR, ERBB2, NRAS, DDR2, TP53, ALK, CTNNB1, MET, AKT1, PTEN and MAP2K1. In subsets of patients, fluorescence in-situ hybridization (FISH) was performed for amplification detection of FGFR1 and MET. We queried the TCGA dataset with respect to the panel used and compared the findings. For the NGM patients, therapy and outcome were also collected.

Results

Beside expected frequencies of TP53, DDR2, PTEN and PIK3CA mutations, we detected EGFR mutations in 3.2% and BRAF mutations in 1.8%. Unlike the TCGA dataset, where the frequencies were 2.8% and 3.9%, respectively, the detected mutations in the NGM cohort consisted of activating mutations (i. e., EGFR del19 and L858R, and BRAF V600E). FISH data revealed a presence of MET amplification in 14.2% and of FGFR1 amplification in 20.0%. The association and correlation of these aberrations with clinical findings and prognosis as well as with PD-L1 expression status and mutational load is still being analyzed. HER2 amplification, which occurred in 2.2% of the TCGA cohort, will be analyzed in a subset of patients.

Conclusions

Our data suggest that the presence of a potential targetable aberration might occur in up to 40% of SqCLC all-comers. Further analyses are warranted in order to characterize SqCLC patients according to their biomarker profiles for potential treatment recommendations.

Clinical trial identification

Legal entity responsible for the study

Lung Cancer Group Cologne, University Hospital Cologne

Funding

Lung Cancer Group Cologne, University Hospital Cologne

Disclosure

J. Wolf: Astrazeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, MSD, Novartis, Pfizer, Roche. All other authors have declared no conflicts of interest.