124P - Driverless lung carcinoma: Impact of expanded RNA and protein-based testing on detection of actionable biomarkers

Date 07 May 2017
Event ELCC 2017
Session Poster Display Session
Topics Lung and other Thoracic Tumours
Presenter Zoran Gatalica
Citation Annals of Oncology (2017) 28 (suppl_2): ii28-ii51. 10.1093/annonc/mdx091
Authors Z. Gatalica1, J. Xiu2, W. Chen2, T. Maney2, A. Voss3, N. Plowman4
  • 1Caris Life Sciences, AZ85040 - Phoenix/US
  • 2Caris Life Sciences, Phoenix/US
  • 3Caris Life Sciences, Basel/CH
  • 4St. Bartholomew's Hospital, London/GB

Abstract

Background

In recent years, massively parallel-gene sequencing (NGS) has improved the detection of targetable mutations in lung cancer (NSCLC). We have identified NSCLC cases that, despite extensive DNA sequencing and targeted in-situ hybridizations (ISH) for ROS1, ALK and cMET alterations, have no druggable target or conventional lung cancer pathogenic mutation identified ("driverless" cancer). Expanded platform testing (RNA and protein-based) was performed on these driverless cases in order to assess the ability of these technologies to identify actionable drug targets.

Methods

A review of 522 NSCLC cases (Caris Life Sciences, Phoenix, AZ) tested with NGS (592 gene sequencing panel, Agilent SureSelectXT; Illumina NextSeq) and ISH yielded 21 patients (F:M=12:9) without characteristic genetic alterations. Expanded testing included an RNA-based fusion panel (52 genes, Archer FusionPlex) and protein-expression (IHC) testing for EGFR, TS and PD-L1.

Results

Expanded platform profiling identified targetable NTRK gene fusions (NTRK3:ETV6 and NTRK1:TPM3) in 2 cases and c-MET exon 14 skipping in 1 case. IHC identified PD-L1 expression in 7 (3 low and 4 high TPS), EGFR over-expression (H-score>200) in 7, and TS under expression in 13 cases. Initial NGS panel identified 2 low allele frequency pathogenic mutations (PIK3CA and GNAS), and 3 gene amplifications (MDM2, CDK4 and CDKN2A), as potential non-characteristic drivers in 4 cases. Total mutational load (TML) range was 1-10/Mb (mean 5.2/Mb).

Conclusions

With the routine use of NGS a small proportion of cases (4.2%) remain without standard biomarker-guided therapy recommendation. They are characterized by a lower TML (5.2/Mb) than reported for NSCLC (e.g. TCGA mean: 8.9/Mb). A significant benefit from expanded multiplatform testing (RNA- and protein-based) included detection of biomarkers for immune check point inhibitors (33% eligible) and targeted therapies (23% eligible: NTRK and c-Met inhibitors). Over-expression of EGFR and under expression of TS (57% and 72%. respectively) could provide additional information for therapy guidance in specific cancer types.

Clinical trial identification

Not applicable

Legal entity responsible for the study

Caris Life Sciences

Funding

Caris Life Sciences

Disclosure

Z. Gatalica, A. Voss: Employment: Caris Life Sciences. J. Xiu, W. Chen, T. Maney: Employment: Caris LIfe Sciences. All other authors have declared no conflicts of interest.