AUTHOR=Pinet Sandra , Durand Stéphanie , Perani Alexandre , Darnaud Léa , Amadjikpe Fifame , Yon Mathieu , Darbas Tiffany , Vergnenegre Alain , Egenod Thomas , Simonneau Yannick , Le Brun-Ly Valérie , Pestre Julia , Venat Laurence , Thuillier Frédéric , Chaunavel Alain , Duchesne Mathilde , Fermeaux Véronique , Guyot Anne , Lacorre Sylvain , Bessette Barbara , Lalloué Fabrice , Durand Karine , Deluche Elise 

TITLE=Clinical management of molecular alterations identified by high throughput sequencing in patients with advanced solid tumors in treatment failure: Real-world data from a French hospital

JOURNAL=Frontiers in Oncology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1104659

DOI=10.3389/fonc.2023.1104659

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>In the context of personalized medicine, screening patients to identify targetable molecular alterations is essential for therapeutic decisions such as inclusion in clinical trials, early access to therapies, or compassionate treatment. The objective of this study was to determine the real-world impact of routine incorporation of FoundationOne analysis in cancers with a poor prognosis and limited treatment options, or in those progressing after at least one course of standard therapy.</p></sec><sec><title>Methods</title><p>A FoundationOneCDx panel for solid tumor or liquid biopsy samples was offered to 204 eligible patients.</p></sec><sec><title>Results</title><p>Samples from 150 patients were processed for genomic testing, with a data acquisition success rate of 93%. The analysis identified 2419 gene alterations, with a median of 11 alterations per tumor (range, 0–86). The most common or likely pathogenic variants were on <italic>TP53</italic>, <italic>TERT</italic>, <italic>PI3KCA</italic>, <italic>CDKN2A/B</italic>, <italic>KRAS</italic>, <italic>CCDN1</italic>, <italic>FGF19</italic>, <italic>FGF3</italic>, and <italic>SMAD4</italic>. The median tumor mutation burden was three mutations/Mb (range, 0–117) in 143 patients with available data. Of 150 patients with known or likely pathogenic actionable alterations, 13 (8.6%) received matched targeted therapy. Sixty-nine patients underwent Molecular Tumor Board, which resulted in recommendations in 60 cases. Treatment with genotype-directed therapy had no impact on overall survival (13 months <italic>vs.</italic> 14 months; p = 0.95; hazard ratio = 1.04 (95% confidence interval, 0.48–2.26)].</p></sec><sec><title>Conclusions</title><p>This study highlights that an organized center with a Multidisciplinary Molecular Tumor Board and an NGS screening system can obtain satisfactory results comparable with those of large centers for including patients in clinical trials.</p></sec>