Usefulness of Two Independent DNA and RNA Tissue-Based Multiplex Assays for the Routine Care of Advanced NSCLC Patients.

Elba Marín ,Roxana Reyes,Silvia Muñoz,Marcelo Sánchez,Antonio Martinez,Pedro Jares,Carlos Cabrera,Miguel Ángel Molina-Vila,Aleix Prat,Alegría Borrás Rodríguez ,Iván Vollmer ,Mireia García ,Ivana Sullivan ,A Arcocha ,S Castillo ,Cristina Teixidó ,Elena Carmona‐Rocha ,Macarmen Rodríguez-Mues ,Núria Viñolas ,Silvia Alós ,Noemı́ Reguart

doi:10.3390/cancers12051124

Abstract

Personalized medicine is nowadays a paradigm in lung cancer management, offering important benefits to patients. This study aimed to test the feasibility and utility of embedding two multiplexed genomic platforms as the routine workup of advanced non-squamous non-small cell lung cancer (NSCLC) patients. Two parallel multiplexed approaches were performed based on DNA sequencing and direct digital detection of RNA with nCounter® technology to evaluate gene mutations and fusions. The results were used to guide genotype-directed therapies and patient outcomes were collected. A total of 224 advanced non-squamous NSCLC patients were prospectively included in the study. Overall, 85% of samples were successfully characterized at DNA and RNA levels and oncogenic drivers were found in 68% of patients, with KRAS, EGFR, METΔex14, BRAF, and ALK being the most frequent (31%, 19%, 5%, 4%, and 4%, respectively). Among all patients with complete genotyping results and follow-up data (n = 156), the median overall survival (OS) was 1.90 years (confidence interval (CI) 95% 1.69–2.10) for individuals harbouring an actionable driver treated with a matched therapy, compared with 0.59 years (CI 95% 0.39–0.79) in those not eligible for any targeted therapy and 0.61 years (CI 95% 0.12–1.10) in patients with no drivers identified (p < 0.001). Integrating DNA and RNA multiplexing technologies into the routine molecular testing of advanced NSCLC patients is feasible and useful and highlights the necessity of widespread integrating comprehensive molecular diagnosis into lung cancer care.

Highlights

The emergence of targeted therapy has revolutionized the management of patients with lung cancer by incorporating tumour molecular analyses into the routine diagnostic and therapeutic process [1]
Between June 2017 and August 2019, a total of 224 advanced non-small cell lung cancer (NSCLC) patients were prospectively diagnosed at our institution
The last follow-up and update of the database was done in November

Summary

Introduction

The emergence of targeted therapy has revolutionized the management of patients with lung cancer by incorporating tumour molecular analyses into the routine diagnostic and therapeutic process [1]. At this time, non-small cell lung cancer (NSCLC) has undergone a paradigm shift from a purely histological to a molecular-based treatment approach, allowing for the selection of patients that would most benefit from targeted therapies, and impacting lung cancer care overall. This is the case of Europeans, who face extreme inequality in access to appropriate molecular diagnosis, even within the same country, with huge differences in the national policies for reimbursement [10]

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