Prognostic value of serial liquid biopsy EGFR mutation monitoring in Hispanic patients with advanced NSCLC treated with osimertinib.
Abstract
e20761 Background: The prognostic role of serial circulating tumor DNA (ctDNA) dynamics during osimertinib treatment has been described mainly in Asian and European populations; however, it remains poorly defined in Hispanic patients with advanced EGFR-mutant non–small cell lung cancer (NSCLC). Our aim was to determine whether serial plasma EGFR testing identifies patients at high risk of early mortality. Methods: This multicenter, retrospective study included 64 Hispanic patients with stage IIIB–IV EGFR-mutant NSCLC treated with first-line osimertinib between 2018 and 2023. Tumor tissue genotyping was performed using hybrid-capture next-generation sequencing. Plasma EGFR mutations were assessed at baseline, week 8, and week 24. Overall survival (OS) and progression-free survival (PFS) were analyzed using Cox models adjusted for p53 status, RAF-pathway alterations, and metastatic burden. Results: The cohort had a median age of 61 years, with 65.6% of patients being female and 56.2% being never-smokers. Sensitizing EGFR mutations consisted mainly of exon 19 deletion (59.4%) and L858R (39.1%). Relevant co-mutations were identified in TP53 (29.7%) and RAF-pathway genes (6.2%). Plasma ctDNA remained positive in 42.2% of patients at week 8 and 22.0% at week 24. Week-8 ctDNA persistence was strongly associated with an inferior OS (HR 9.36, 95% CI 3.80–23.03, p < 0.001) after multivariable adjustment. Week-24 positivity also predicted worse OS (HR 3.34, 95% CI 1.13–9.89, p = 0.02). ctDNA status at week 8 or 24 was not significantly associated with PFS. Patients with TP53 or RAF pathway mutations demonstrated higher rates of molecular persistence. Conclusions: In Hispanic patients receiving Osimertinib, ctDNA positivity at 8-24 weeks is able to identify patients with poor survival outcomes. ctDNA monitoring may provide an early, non-invasive biomarker to guide treatment intensification and trial enrollment in EGFR-mutant NSCLC.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (20)
Juan Manuel Garzon-Dangond
Atlantic Health System - Overlook Medical Center, Summit, NJ
Andrés Felipe Cardona
Arnaud Scherpereel, MD, PhD, CHU Lille, Univ. Lille, Inserm, U1366-UMR9020—CRCLille—Cancer Research Center of Lille, OncoThAI, ONCOLille, Lille, France; Aaron S. Mansfield, MD, Mayo Clinic, Rochester, MN; Francesco Grossi, MD, Medical Oncology Division, Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy; Sanjay Popat, PhD, FRCP, The Royal Marsden Hospital, London, United Kingdom; Paul Baas, MD, PhD, The Netherlands Cancer Institute and Leiden University Medical Center, Amsterdam, the Netherlands; Anna K. Nowak, PhD, MBBS, University of Western Australia, Perth, WA, Australia; Anne S. Tsao, MD, MBA, University of Texas MD Anderson Cancer Center, Houston, TX; Nobukazu Fujimoto, MD, PhD, Okayama Rosai Hospital, Okayama, Japan; Solange Peters, MD, PhD, Lausanne University Hospital, Lausanne, Switzerland; Yolanda Bautista Aragon, MD, Centro Médico Nacional Siglo XXI, Mexico City, Mexico; Toby Talbot, MD, The Sunrise Centre, Royal Cornwall Hospitals NHS Trust, Truro, Unite...
Jairo Andrés Zuluaga
Luis Carlos Sarmiento Angulo Cancer Treatment and Research Center - CTIC, Bogota, Colombia
Leonardo Rojas
Nicolle Wagner-Gutiérrez
Universidad de los Andes, Bogota, Colombia
Alejandro Ruiz-Patiño
Foundation for Clinical and Applied Cancer Research - FICMAC, Bogotá, Colombia
Diego Chamorro
Fundación para la Investigación Clínica y aplicada del Cancer (FICMAC), Bogotá, Colombia
July Rodriguez
Fundación para la Investigación Clínica y Molecular Aplicada del Cáncer (FICMAC), Bogotá, Colombia
Dora Lucia Vallejo-Ardila
Fundación de Investigación Clínica y Molecular Aplicada del Cáncer FICMAC, Bogota, Colombia
Lucia Viola
Fundacion Neumologica Colombia - Luis Carlos Sarmiento Angulo Cancer Treatment and Research Center, Bogotá, Colombia
Stella Martinez
Luis Carlos Sarmiento Angulo Cancer Treatment and Research Center (CTIC), Bogotá, Colombia
Carlos Carvajal
Luis Carlos Sarmiento Angulo Cancer Treatment and Research Center (CTIC), Bogotá, Colombia
Pilar Archila
Fundación de Investigación Clínica y Molecular Aplicada del Cáncer FICMAC, Bogotá, Colombia
Juan Esteban Garcia-Robledo
Mayo Clinic Arizona, Scottsdale, AZ
Elvira Jaller
Thoracic Oncology Unit, National Cancer Institute (INCan), Mexico City, Mexico
Claudio Martin
Instituto Alexander Fleming, Buenos Aires
Luis Corrales
Centro de Investigacion y Manejo del Cancer (CIMCA), San José, Costa Rica
Christian Diego Rolfo
Center for Thoracic Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY
Rafael Rosell
Oscar Arrieta