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  P73 - Tumor Biology and Systems Biology - Basic and Translational Science - RTK/FGFR (ID 209)

  • Event: WCLC 2020
  • Type: Posters
  • Track: Tumor Biology and Systems Biology - Basic and Translational Science
  • Presentations: 1
  • Moderators:
  • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall

  • 35890

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    P73.02 - The Landscape of FGFR Alteration in Chinese Patients with Lung Cancer (ID 1500)

    00:00 - 00:00  |  Presenting Author(s): Huilin Wang
    • Abstract

    Introduction
    

    Fibroblast growth factor (FGF) family being part of the receptor tyrosine kinase (RTK) families exerts their functions through four highly conserved tyrosine kinase receptors (including FGFR1, FGFR2, FGFR3 or FGFR4). Aberrant activation of the FGFR signaling pathway by genetic alteration (GA) seems to be mainly responsible for the neoplastic development in many cancers including non‐small cell lung cancer (NSCLC). These make FGFR family genes to be highly potential therapy target in cancers and several inhibitors targeting FGFR have demonstrated clinical benefit in cancer patients, such as Erdafitinib in metastatic urothelial cancers. However, the landscape of FGFR genes in Chinese patients with lung cancer has not been well understood and the correlation between FGFR genetic alterations and immune checkpoint inhibitors (ICIs) response in NSCLC remains unclear.

    Methods
    

    Formalin-fixed, paraffin-embedded (FFPE) tumor samples were collected from 6275 Chinese patients with lung cancer and subjected to a clinical-grade next-generation sequencing (NGS)-based 450 gene panel test from December 2017 to January 2019. GAs including single nucleotide variations, short and long insertions/deletions, copy number variations, and gene rearrangements were assessed. Genomic data and ICIs treatment outcome of 2 cohorts of NSCLC patients were derived from The Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering Cancer Center (MSKCC) databases.

    Results
    

    Genomic alterations (GAs) of FGFR1-4 were detected in 5.3% of patients with lung cancer in the OrigiMed database, including 2.5% FGFR1 GAs, 1.2% FGFR4 GAs, 0.9% FGFR3 GAs, and 0.9% FGFR2 GAs. The frequency of FGFR alteration was highest in squamous cell lung carcinoma (15.9%), followed by small cell lung cancer (6.6%) and lung adenocarcinoma (3.6%). Amplification was the most common type of FGFR variation, which accounted for 45.9% of all FGFR GAs, followed by substitution/indels (45%), fusion/rearrangements (7.8%) and truncations (1.3%). FGFR3-TACC3 was the most common type of FGFR translocations (34.6%) and SNTG1-FGFR1, CADPS2-FGFR1 and UGP2-FGFR2 were novel types of FGFR fusion/rearrangement identified in our cohort. The most common co-alterations associated with FGFR alterations were TP53 (76.9%), EGFR (33.3%), LRP1B (26.1%), CDKN2A (20%) and PIK3CA (19.5%). Compared with wild-type (WT), FGFR1-4 GAs were associated with a significantly higher tumor mutational burden (TMB) (10 vs. 4.6 muts/Mb, respectively, p<0.001). Survival analysis from 2 independent cohorts confirmed that FGFR4 GAs but not FGFR1-3 were associated with longer progression free survival (PFS) (13.17 months vs 3.17 months, respectively, p=0.025) and higher proportion of durable clinical benefit (DCB) (80% vs 29.3%, respectively, p=0.03) of immune checkpoint inhibitors treatments. Furthermore, FGFR4 GAs were an independent risk factor of PFS (HR: 0.22, 95%CI: 0.055-0.92, p=0.037) and overall survival (OS) (HR: 0.23, 95%CI: 0.057-0.92, p=0.038).

    Conclusion
    

    FGFR-alterations were found in 5.3% of Chinese patients with lung cancers. Lung cancer patients with FGFR alterations were associated with an increased TMB but only those harboring FGFR4 GAs might experience favorable response to ICIs. This suggests that GAs of FGFR4 may have implications as a biomarker for guiding ICI treatment.