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    Association details:
    Biomarker:KEAP1 mutation
    Cancer:Non Small Cell Lung Cancer
    Drug Class:Immunotherapy
    Direction:Resistant
    Evidence:
    Evidence Level:
    Resistant: C3 – Early Trials
    Source:
    J Thorac Oncol
    Title:

    Microsatellite instability and mismatch repair deficiency define a distinct subset of lung cancers characterized by smoking exposure, high tumor mutational burden and recurrent somatic MLH1 inactivation.

    Published date:
    10/12/2023
    Excerpt:
    In NSCLC, STK11, KEAP1, and JAK1 were mutated in non-responders but wild type in responders.
    DOI:
    https://doi.org/10.1016/j.jtho.2023.10.004
    Evidence Level:
    Resistant: C3 – Early Trials
    Source:
    Ann Oncol
    Title:

    Clonal KEAP1 mutations with loss of heterozygosity share reduced immunotherapy efficacy and low immune cell infiltration in lung adenocarcinoma.

    Published date:
    12/13/2022
    Excerpt:
    In the ICI-treated MSK/Rome discovery cohort, predicted KEAP1 C-LOH mutations were associated with shorter progression-free survival (PFS) and overall survival (OS) compared to KEAP1 wild-type cases (PFS log-rank P=0.001; OS log-rank P<0.001).
    DOI:
    https://doi.org/10.1016/j.annonc.2022.12.002
    Evidence Level:
    Resistant: C3 – Early Trials
    Source:
    Lung Cancer
    Title:

    STK11 and KEAP1 mutations in non-small cell lung cancer patients: descriptive analysis and prognostic value among Hispanics (STRIKE registry-CLICaP)

    Published date:
    06/20/2022
    Excerpt:
    This retrospective study analyzed a cohort of Hispanic patients (N=103) diagnosed with mNSCLC from the US and seven Latin American countries (LATAM) treated with immune checkpoint inhibitors (ICI) alone or in combination...When we compared the cohorts A and B, OS was significantly shorter for patients carrying STK1 [STK11Mut 14.2 months versus STK11Wt 27.0 months (p=0.0001)] or KEAP1 [KEAP1Mut 12.0 months versus KEAP1Wt 24.4 months (p=0.005)] mutations.
    DOI:
    https://doi.org/10.1016/j.lungcan.2022.06.010
    Evidence Level:
    Resistant: C3 – Early Trials
    Source:
    ASCO 2021
    Title:

    The prognostic impact of KRAS, TP53, STK11 and KEAP1 mutations and the influence of the NLR in NSCLC patients treated with immunotherapy.

    Published date:
    05/19/2021
    Excerpt:
    We conducted a retrospective study including all consenting patients with NSCLC treated with ICIs...The presence of STK11 and/or KEAP1 mutations was associated with a negative impact on survival when compared with wild-type (median OS 7.4 vs 20.4 months, p = 0.001)....The STK11 and KEAP1 mutations are significant adverse predictors of ICI therapy benefit.
    DOI:
    10.1200/JCO.2021.39.15_suppl.e21010
    Evidence Level:
    Resistant: C3 – Early Trials
    Source:
    ESMO 2020
    Title:

    107P - Immune Checkpoint Inhibitor (ICPI) resistance genes STK11 and KEAP1: A comparative Comprehensive Genomic Profiling (CGP) study

    Published date:
    09/14/2020
    Excerpt:
    CONTRADICTING EVIDENCE: NSCLC was the predominant disease type with both SK11mut (65%) and KEAP1mut (55%) cases....In addition, STK11mut and KEAP1mut tumors feature biomarkers predictive of ICPI benefit despite the likelihood of resistance and a paucity of targeted therapy opportunities.
    Evidence Level:
    Resistant: C3 – Early Trials
    Source:
    ASCO 2020
    Title:

    KEAP1/NFE2L2 as a prognostic biomarker on immunotherapy and correlation with immune infiltrates in non-small cell lung cancer (NSCLC).

    Published date:
    05/13/2020
    Excerpt:
    The OAK and POPLAR study cohort of NSCLC patients showed that KEAP1/NFE2L2 MUT was associated with poorer overall survival (OS), and progression-free survival (PFS) (OS: HR = 1.7, P < 0.001; PFS:HR = 1.4, P < 0.001) on immunotherapy, even after EGFR and ALK mutations were excluded, significant difference can also be gained (OS:HR = 1.8, P < 0.001; PFS:HR = 1.5, P < 0.001).
    DOI:
    10.1200/JCO.2020.38.15_suppl.e21551