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    Association details:
    Biomarker:EGFR mutation + HLA-DRB5 rs1071748
    Cancer:Lung Cancer
    Drug Class:EGFR inhibitor
    Direction:Resistant
    Evidence:
    Evidence Level:
    Resistant: C3 – Early Trials
    Source:
    Mol Cancer
    Title:

    Durable response of lung carcinoma patients to EGFR tyrosine kinase inhibitors is determined by germline polymorphisms in some immune-related genes

    Published date:
    07/29/2023
    Excerpt:
    We sequenced tumor exomes from 135 lung cancer patients (79 with EGFR-wildtype (WT), 56 with EGFR-mutant tumors) enrolled in the ALCAPONE trial...Seven polymorphisms spread along three other genes: HLA-DRB5, KIR3DL1, and KIR3DL2, were associated with a worse PFS in patients receiving an EGFR TKI treatment. These included the following three variants in the HLA-DRB5 gene: rs1071748 (c.119A > G, p.(Asp40Gly)), rs184278615 (c.160C > T, p.(Arg54Trp)), and rs201469165 (c.163 T > A, p.(Phe55Ile)) (HR = 2.52 [1.24–5.09] p = 0.008, HR = 3.49 [1.58–7.68] p = 0.001, and HR = 2.78 [1.31–5.89] p = 0.005, respectively...
    DOI:
    https://doi.org/10.1186/s12943-023-01829-4
    Trial ID:
    ALCAPONE