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Ref Type Journal Article
PMID (32312757)
Authors Papillon-Cavanagh S, Doshi P, Dobrin R, Szustakowski J, Walsh AM
Title STK11 and KEAP1 mutations as prognostic biomarkers in an observational real-world lung adenocarcinoma cohort.
Journal Vol Issue Date Pages Journal Short Title
ESMO open 5 2 2020 04 ESMO Open
URL
Abstract Text Somatic mutations in STK11 and KEAP1, frequently comutated in non-squamous non-small cell lung cancer (NSQ NSCLC), have been associated with poor response to immune checkpoint blockade (ICB). However, previous reports lack non-ICB controls needed to properly ascertain the predictive nature of those biomarkers. The objective of this study was to evaluate the predictive versus prognostic effect of STK11 or KEAP1 mutations in NSQ NSCLC.Patients diagnosed with stage IIIB, IIIC, IVA or IVB NSQ NSCLC from a real-world data cohort from the Flatiron Health Network linked with genetic testing from Foundation Medicine were retrospectively assessed. Real-world, progression-free survival (rwPFS) and overall survival (OS) were calculated from time of initiation of first-line treatment.We analysed clinical and mutational data for 2276 patients including patients treated with anti-programmed death-1 (PD-1)/anti-programmed death ligand 1 (PD-L1) inhibitors at first line (n=574). Mutations in STK11 or KEAP1 were associated with poor outcomes across multiple therapeutic classes and were not specifically associated with poor outcomes in ICB cohorts. There was no observable interaction between STK11 mutations and anti-PD-1/anti-PD-L1 treatment on rwPFS (HR, 1.05; 95% CI 0.76 to 1.44; p=0.785) or OS (HR, 1.13; 95% CI 0.76 to 1.67; p=0.540). Similarly, there was no observable interaction between KEAP1 mutations and treatment on rwPFS (HR, 0.93; 95% CI 0.67 to 1.28; p=0.653) or OS (HR, 0.98; 95% CI 0.66 to 1.45; p=0.913).Our results show that STK11-KEAP1 mutations are prognostic, not predictive, biomarkers for anti-PD-1/anti-PD-L1 therapy.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
KEAP1 mut STK11 mut lung adenocarcinoma not predictive unspecified PD-L1 antibody Clinical Study - Cohort Actionable In a clinical study, lung adenocarcinoma patients harboring both a KEAP1 mutation and STK11 mutation demonstrated a shorter progression free survival compared to patients with wild-type KEAP1 and wild-type STK11 when treated with an unspecified PD-L1 antibody treatment, but when compared to other treatments, all were associated with shorter progression free survival (PMID: 32312757). 32312757
STK11 mutant lung adenocarcinoma not applicable N/A Clinical Study Emerging In clinical studies, STK11 mutations were associated with an inferior prognosis in patients with lung adenocarcinoma (PMID: 32312757, PMID: 32413741). 32413741 32312757
KEAP1 mutant lung adenocarcinoma not predictive unspecified PD-1 antibody Clinical Study - Cohort Actionable In a clinical study, lung adenocarcinoma patients harboring a KEAP1 mutation demonstrated a shorter progression free survival compared to patients with wild-type KEAP1 when treated with an unspecified PD-1 antibody, but when compared to other treatments, all were associated with shorter progression free survival (PMID: 32312757). 32312757
STK11 mutant lung adenocarcinoma not predictive unspecified PD-L1 antibody Clinical Study - Cohort Actionable In a clinical study, lung adenocarcinoma patients harboring an STK11 mutation demonstrated a shorter progression free survival compared to patients with wild-type STK11 when treated with an unspecified PD-L1 antibody treatment, but when compared to other treatments, all were associated with shorter progression free survival (PMID: 32312757). 32312757
STK11 mutant lung adenocarcinoma not predictive unspecified PD-1 antibody Clinical Study - Cohort Actionable In a clinical study, lung adenocarcinoma patients harboring an STK11 mutation demonstrated a shorter progression free survival compared to patients with wild-type STK11 when treated with an unspecified PD-1 antibody treatment, but when compared to other treatments, all were associated with shorter progression free survival (PMID: 32312757). 32312757
KEAP1 mutant lung adenocarcinoma not predictive unspecified PD-L1 antibody Clinical Study - Cohort Actionable In a clinical study, lung adenocarcinoma patients harboring a KEAP1 mutation demonstrated a shorter progression free survival compared to patients with wild-type KEAP1 when treated with an unspecified PD-L1 antibody, but when compared to other treatments, all were associated with shorter progression free survival (PMID: 32312757). 32312757
KEAP1 mut STK11 mut lung adenocarcinoma not predictive unspecified PD-1 antibody Clinical Study - Cohort Actionable In a clinical study, lung adenocarcinoma patients harboring both a KEAP1 mutation and STK11 mutation demonstrated a shorter progression free survival compared to patients with wild-type KEAP1 and wild-type STK11 when treated with an unspecified PD-1 antibody treatment, but when compared to other treatments, all were associated with shorter progression free survival (PMID: 32312757). 32312757