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RESEARCH PRODUCT
LungBEAM: A prospective multicenter study to monitor stage IV NSCLC patients with EGFR mutations using BEAMing technology
José Luis González-larribaJose Manuel TrigoNuria ViñolasRosario Garcίa-campeloAngel ArtalJoaquim Bosch-barreraTeresa MoranCarlos CampsEnriqueta FelipBartomeu MassutiJosé Miguel Sánchez-torresAlfredo ParedesLuis Paz-aresMarta López-breaJosé PalaciosAmelia InsaPilar GarridoDolores IslaMargarita MajemOscar Juansubject
OncologyMaleCancer ResearchPulmons - Càncer - PrognosiLung Neoplasms:técnicas de investigación::técnicas genéticas::análisis de secuencias::análisis de secuencias de ADN::análisis de mutaciones del ADN [TÉCNICAS Y EQUIPOS ANALÍTICOS DIAGNÓSTICOS Y TERAPÉUTICOS]medicine.disease_causeBEAMingExonnon-small cell lung carcinomaInterquartile rangeCarcinoma Non-Small-Cell LungEpidermal growth factor receptorProspective StudiesRC254-282Research ArticlesMutationmedicine.diagnostic_testbiologyHazard ratioNeoplasms. Tumors. Oncology. Including cancer and carcinogens:Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma Bronchogenic::Carcinoma Non-Small-Cell Lung [DISEASES]ErbB ReceptorsOncology:Investigative Techniques::Genetic Techniques::Sequence Analysis::Sequence Analysis DNA::DNA Mutational Analysis [ANALYTICAL DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT]FemaleADN - AnàlisiResearch Articlemedicine.medical_specialty:Otros calificadores::/diagnóstico [Otros calificadores]Internal medicineBiopsymedicineHumansRadiology Nuclear Medicine and imagingLiquid biopsyAgedliquid biopsybusiness.industryClinical Cancer Research:neoplasias::neoplasias por localización::neoplasias torácicas::neoplasias del tracto respiratorio::neoplasias pulmonares::neoplasias de los bronquios::carcinoma broncogénico::carcinoma de pulmón de células no pequeñas [ENFERMEDADES]EGFR mutationsConfidence intervalnon‐small cell lung carcinomarespiratory tract diseases:Neoplasms [DISEASES]Mutationbiology.proteinbusinessPulmons - Càncer - Tractamentdescription
Abstract Objectives The aim of LungBEAM was to determine the value of a novel epidermal growth factor receptor (EGFR) mutation test in blood based on BEAMing technology to predict disease progression in advanced non‐small cell lung cancer (NSCLC) patients treated with first‐ or second‐generation EGFR‐tyrosine kinase inhibitors (EGFR‐TKIs). Another goal was to monitor the dynamics of EGFR mutations, as well as to track EGFR exon 20 p.T790M (p.T790M) resistance during treatment, as critical indicators of therapeutic efficacy and patient survival. Methods Stage IV NSCLC patients with locally confirmed EGFR‐TKI sensitizing mutations (ex19del and/or L858R) in biopsy tissue who were candidates to receive first‐ or second‐generation EGFR‐TKI as first‐line therapy were included. Plasma samples were obtained at baseline and every 4 weeks during treatment until a progression‐free survival (PFS) event or until study completion (72‐week follow‐up). The mutant allele fraction (MAF) was determined for each identified mutation using BEAMing. Results A total of 68 of the 110 (61.8%) patients experienced a PFS event. Twenty‐six patients (23.6%) presented with an emergent p.T790M mutation in plasma at some point during follow‐up, preceding radiologic progression with a median of 76 (interquartile ratio: 54–111) days. Disease progression correlated with the appearance of p.T790M in plasma with a hazard ratio (HR) of 1.94 (95% confidence interval [CI], 1.48–2.54; p < 0.001). The HR for progression in patients showing increasing plasma sensitizing mutation levels (positive MAF slope) versus patients showing either decreasing or unchanged plasma mutation levels (negative or null MAF slopes) was 3.85 (95% CI, 2.01–7.36; p < 0.001). Conclusion Detection and quantification of EGFR mutations in circulating tumor DNA using the highly sensitive BEAMing method should greatly assist in optimizing treatment decisions for advanced NSCLC patients.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2021-07-23 |