Author of

• 20039

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  Poster Display Session (ID 63)

  • Event: ELCC 2017
  • Type: Poster Display Session
  • Track:
  • Presentations: 2
  • Moderators:
  • Coordinates: 5/07/2017, 12:30 - 13:00, Hall 1

  • 19880

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    124P - Driverless lung carcinoma: Impact of expanded RNA and protein-based testing on detection of actionable biomarkers (ID 396)

    12:30 - 13:00  |  Author(s): Z. Gatalica
    • 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.
    
    

  • 19905

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    149P - PD-L1 expression patterns in the metastatic tumors to the lung: A comparative study with the primary non-small cell lung cancer (ID 251)

    12:30 - 13:00  |  Author(s): Z. Gatalica
    • Abstract

    Background:
    Immune check point inhibitors (anti-PD-1/PD-L1) therapy has revolutionized cancer treatment of several, advanced and chemotherapy resistant malignancies. PD-L1 expression on tumor (TC) and/or inflammatory cells (IC) has been associated with a more favorable therapy response. We compared PD-L1 distribution in a large cohort of advanced tumors metastatic to the lungs and compared it with the primary lung non-small cell carcinomas (NSCLC).
    
    Methods:
    The study groups included 176 metastatic cancers and 81 NSCLC. Expression of PD-L1 was assessed using immunohistochemistry (SP142, Ventana). PD-L1 positivity was defined as 2+ intensity at ≥ 5% in TC or IC cells. All cases were further stratified into 4 categories based on the expression presence or absence of PD-L1 expression on tumor or IC cells. PD-L1 expression was correlated with total mutational load (TML) measured in tumors using NGS.
    
    Results:
    Overall TC PD-L1 positivity was significantly higher in NSCLC compared with metastatic tumors (28% vs. 14%, p = 0.009) although some metastatic cancers (e.g. triple-negative breast and head/neck carcinomas, melanoma) exhibited higher TC PD-L1 expression. In contrast, overall IC PD-L1 expression was predominantly observed in metastatic tumors (28% vs. 0%, p < 0.001). The IC PD-L1 expression ranged from 0% for metastatic renal cell carcinomas to 36-38% in the metastatic breast and colon carcinomas and melanoma. Consequently, the stratification based on PD-L1 distribution (TC vs. IC), resulted in significantly different patterns between the primary and metastatic tumors (p < 0.001, Table). Mean TML (±SD) for NSCLC (10±5.6) differed significantly from metastatic carcinomas from other sites (6.6±2.7) (p = 0.013).
    
    Conclusions:
    Our study indicate that a substantial proportion of metastatic tumors to the lung exhibit PD-L1 expression on either tumor or inflammatory (immune) cells and are potentially amenable for the treatment with immune check point inhibitors.rnTable: 149Prn

    rnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrn

    Histotypes	TME categories (PD-L1 expression)				Total
    	TC+/IC+	TC-/IC-	TC+/IC-	TC-/IC+
    NSCLC	0	58	23	0	81
    Metastatic tumors	8	111	16	41	176
    Total	8	169	39	41	257

    rn
    
    Clinical trial identification:
    
    
    Legal entity responsible for the study:
    None
    
    Funding:
    Caris Life Sciences
    
    Disclosure:
    Z. Gatalica: Employee of Caris Life Sciences. J. Senarathne: Jude Senarathne is an employee of Caris Life Sciences. S. Vranic: Received honoraria from Caris Life Sciences.