Ramon Palmero1, Alvaro Taus2,3, Santiago Viteri4, Margarita Majem5, Enric Carcereny6, Javier Garde-Noguera5, Enriqueta Felip7, Ernest Nadal1, Andrea Malfettone8, Miguel Sampayo8, François Riva8, Rebecca J Nagy9, Richard B Lanman9, Iris Faull9, Daniel Dix9, Niki Karachaliou10, Rafael Rosell10. 1. ICO Bellvitge, Hospitalet Llobregat/Spain. 2. Hospital del Mar, Barcelona, Spain. 3. Universidad Autónoma de Barcelona (UAB), Barcelona, Spain. 4. Quirón Salud-Dexeus University Institute, IOR, Medical Oncology Department, Barcelona, Spain. 5. Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 6. Institut Català d'Oncologia Badalona-Hospital Germans Trias i Pujol B-ARGO, Badalona, Spain. 7. Vall d'Hebron Institute of Oncology, Barcelona, Spain. 8. Medica Scientia Innovation Research-MEDSIR, Barcelona, Spain and Ridgewood, NJ. 9. Guardant Health, South San Francisco, CA. 10. Catalan Institute of Oncology, Hospital Germans Trias I Pujol, Badalona, Spain.
Abstract
PURPOSE: Treatment guidelines for advanced non-small-cell lung cancer (aNSCLC) recommend broad molecular profiling for targeted therapy selection. This study prospectively assessed comprehensive next-generation sequencing (NGS) of cell-free circulating tumor DNA (cfDNA) compared with standard-of-care (SOC) tissue-based testing to identify guideline-recommended alterations in aNSCLC. PATIENTS AND METHODS: Patients with treatment-naïve aNSCLC were tested using a well-validated NGS cfDNA panel, and results were compared with SOC tissue testing. The primary objective was noninferiority of cfDNA vs. tissue analysis for the detection of two guideline-recommended biomarkers (EGFR and ALK) and an additional six actionable biomarkers. Secondary analyses included tissue versus cfDNA biomarker discovery, overall response rate (ORR), progression-free survival (PFS) to targeted therapy, and positive predictive value (PPV) of cfDNA. RESULTS: The primary objective was met with cfDNA identifying actionable mutations in 46 patients versus 48 by tissue (P < .05). In total, 0/186 patients were genotyped for all eight biomarkers with tissue, compared with 90.8% using cfDNA. Targetable alterations or KRAS were identified in 80.7% when cfDNA was used first versus 57.1% when tissue was used first. PPV for cfDNA-detected EGFR was 100.0% (25/25). ORR and PFS in patients receiving targeted therapy based on tissue or cfDNA were similar to those previously reported. CONCLUSION: This prospective study confirms a previous report that comprehensive cfDNA testing is noninferior to SOC tissue testing in detecting aNSCLC-recommended biomarkers. Furthermore, cfDNA-based first-line therapy produced outcomes similar to tissue-based testing, demonstrating the clinical utility of comprehensive cfDNA genotyping as the initial genotyping modality in patients with treatment-naïve aNSCLC when tissue is insufficient or when all actionable biomarkers cannot be rapidly assessed.
PURPOSE: Treatment guidelines for advanced non-small-cell lung cancer (aNSCLC) recommend broad molecular profiling for targeted therapy selection. This study prospectively assessed comprehensive next-generation sequencing (NGS) of cell-free circulating tumor DNA (cfDNA) compared with standard-of-care (SOC) tissue-based testing to identify guideline-recommended alterations in aNSCLC. PATIENTS AND METHODS: Patients with treatment-naïve aNSCLC were tested using a well-validated NGS cfDNA panel, and results were compared with SOC tissue testing. The primary objective was noninferiority of cfDNA vs. tissue analysis for the detection of two guideline-recommended biomarkers (EGFR and ALK) and an additional six actionable biomarkers. Secondary analyses included tissue versus cfDNA biomarker discovery, overall response rate (ORR), progression-free survival (PFS) to targeted therapy, and positive predictive value (PPV) of cfDNA. RESULTS: The primary objective was met with cfDNA identifying actionable mutations in 46 patients versus 48 by tissue (P < .05). In total, 0/186 patients were genotyped for all eight biomarkers with tissue, compared with 90.8% using cfDNA. Targetable alterations or KRAS were identified in 80.7% when cfDNA was used first versus 57.1% when tissue was used first. PPV for cfDNA-detected EGFR was 100.0% (25/25). ORR and PFS in patients receiving targeted therapy based on tissue or cfDNA were similar to those previously reported. CONCLUSION: This prospective study confirms a previous report that comprehensive cfDNA testing is noninferior to SOC tissue testing in detecting aNSCLC-recommended biomarkers. Furthermore, cfDNA-based first-line therapy produced outcomes similar to tissue-based testing, demonstrating the clinical utility of comprehensive cfDNA genotyping as the initial genotyping modality in patients with treatment-naïve aNSCLC when tissue is insufficient or when all actionable biomarkers cannot be rapidly assessed.
Authors: Pedro Barrios-Bernal; Zyanya Lucia Zatarain-Barrón; Norma Hernández-Pedro; Mario Orozco-Morales; Alejandra Olivera-Ramírez; Federico Ávila-Moreno; Ana Laura Colín-González; Andrés F Cardona; Rafael Rosell; Oscar Arrieta Journal: Pharmaceuticals (Basel) Date: 2022-06-24