Dataset Information

STK11 and KEAP1 mutations as prognostic biomarkers in an observational real-world lung adenocarcinoma cohort.

ABSTRACT: INTRODUCTION: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. METHODS: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. RESULTS: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). CONCLUSION:Our results show that STK11-KEAP1 mutations are prognostic, not predictive, biomarkers for anti-PD-1/anti-PD-L1 therapy.

SUBMITTER: Papillon-Cavanagh S

PROVIDER: S-EPMC7199918 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Publications

<i>STK11</i> and <i>KEAP1</i> mutations as prognostic biomarkers in an observational real-world lung adenocarcinoma cohort.

Papillon-Cavanagh Simon S Doshi Parul P Dobrin Radu R Szustakowski Joseph J Walsh Alice M AM

ESMO open 20200401 2

<h4>Introduction</h4>Somatic mutations in <i>STK11</i> and <i>KEAP1</i>, 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 <i>STK11</i> or <i>KEAP1</i> mutations in NSQ NSCLC.<h4>Methods</h ...[more]

PMID: 32312757

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Project description:IntroductionMigraine is a disabling, recurrent headache disorder with complex comorbidities. Conventional treatments for migraine are unsatisfactory, with side effects and limited effectiveness. Chinese herbal medicine (CHM) has been used as an alternative or complementary treatment option for migraine in China. Currently, the existing evidence of benefit of CHM for migraine has been generated from randomised clinical trials using standardised intervention with a focus on internal validity hence with limited external validity. Moreover, CHM individualised intervention design, patients' preferences and concerns, and clinicians' experience are critical to clinical decision making and therapeutic success. This real-world observational study aims to gather practice-based evidence of effects and safety of CHM for migraine in the context of integrating Chinese medicine diagnostic procedures, patients' preferences and matters relevant to clinical decision making.Methods and analysisThe study is being undertaken at the Guangdong Provincial Hospital of Chinese Medicine (GPHCM) from December 2020 to May 2022. We anticipate that approximately 400 adult migraineurs will be enrolled and observed on their migraine severity, analgesic consumption, quality of life, anxiety, depression and insomnia at baseline and then every four weeks over 12 weeks. Treatments, diagnostic information, and patient-reported most bothersome symptoms will be collected from patient clinical records. Patient's demographic data, preferences and concerns on CHM treatments will also be gathered at baseline and be analysed. Factors related to clinical outcomes will be explored with multiple correlation and multivariable regression analyses. Effects of CHM will be evaluated using generalised estimated equation, based on clinical outcome data.DiscussionThis study will provide comprehensive evidence of CHM for migraine in the context of evidence-based practice.Trial registration numberChiCTR2000041003.

Dataset Information

STK11 and KEAP1 mutations as prognostic biomarkers in an observational real-world lung adenocarcinoma cohort.

Publications

<i>STK11</i> and <i>KEAP1</i> mutations as prognostic biomarkers in an observational real-world lung adenocarcinoma cohort.

Similar Datasets

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