TY - JOUR
T1 - Clinical utility of circulating tumor DNA sequencing with a large panel
T2 - a National Center for Precision Medicine (PRISM) study
AU - Bayle, A
AU - Belcaid, L
AU - Aldea, M
AU - Vasseur, D
AU - Peyraud, F
AU - Nicotra, C
AU - Geraud, A
AU - Sakkal, M
AU - Seknazi, L
AU - Cerbone, L
AU - Blanc-Durand, F
AU - Hadoux, J
AU - Mosele, F
AU - Tagliamento, M
AU - Bernard-Tessier, A
AU - Verret, B
AU - Smolenschi, C
AU - Clodion, R
AU - Auger, N
AU - Martin Romano, P
AU - Gazzah, A
AU - Ngo Camus, M
AU - Micol, J
AU - Caron, O
AU - Hollebecque, A
AU - Loriot, Y
AU - Besse, B
AU - Lacroix, L
AU - Rouleau, E
AU - Ponce, S
AU - Soria, J C
AU - Barlesi, F
AU - Andre, F
AU - Italiano, A
N1 - Copyright © 2023. Published by Elsevier Ltd.
PY - 2023/4
Y1 - 2023/4
N2 - BACKGROUND: Circulating tumor DNA (ctDNA) sequencing is a promising approach for tailoring therapy in patients with cancer. We report hereby the results from a prospective study where we investigated the impact of comprehensive molecular profiling of ctDNA in patients with advanced solid tumors.PATIENTS AND METHODS: Genomic analysis was performed using the FoundationOne Liquid CDx Assay [324 genes, tumor mutational burden (TMB), microsatellite instability status]. Each individual genomic report was reviewed and discussed weekly by a multidisciplinary tumor board (MTB). Actionable targets were classified by ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) tier leading to molecular-based treatment suggestions wherever it was possible.RESULTS: Between December 2020 and November 2021, 1772 patients with metastatic solid tumors underwent molecular profiling. Median time to assay results was 12 days. Results were contributive for 1658 patients (94%). At least one actionable target was detected in 1059 patients (64%) with a total of 1825 actionable alterations including alteration of the DNA damage repair response pathway (n = 336, 18%), high TMB (>16 mutations/Mb; n = 243, 13%), PIK3CA mutations (n = 150, 8%), ERBB family pathway alterations (n = 127, 7%), PTEN alterations (n = 95, 5%), FGFR alterations (n = 67, 4%) and MET activations (n = 13, 0.7%). The MTB recommended a matched therapy for 597 patients (56%) with a total of 819 therapeutic orientations: clinical trials (n = 639, 78%), off-label/compassionate use (n = 81, 10%), approved drug (n = 51, 6%), and early access program (n = 48, 6%). In total, 122 patients (21%) were treated. Among the assessable patients (n = 107), 4 (4%) had complete response, 35 (33%) had partial response, 27 (25%) had stable disease, and 41 (38%) a progressive disease as best response. The median progression-free survival and median overall survival were 4.7 months (95% confidence interval 2.7-6.7 months) and 8.3 months (95% confidence interval 4.7-11.9 months) respectively.CONCLUSIONS: ctDNA sequencing with a large panel is an efficient approach to match patients with advanced cancer with targeted therapies.
AB - BACKGROUND: Circulating tumor DNA (ctDNA) sequencing is a promising approach for tailoring therapy in patients with cancer. We report hereby the results from a prospective study where we investigated the impact of comprehensive molecular profiling of ctDNA in patients with advanced solid tumors.PATIENTS AND METHODS: Genomic analysis was performed using the FoundationOne Liquid CDx Assay [324 genes, tumor mutational burden (TMB), microsatellite instability status]. Each individual genomic report was reviewed and discussed weekly by a multidisciplinary tumor board (MTB). Actionable targets were classified by ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) tier leading to molecular-based treatment suggestions wherever it was possible.RESULTS: Between December 2020 and November 2021, 1772 patients with metastatic solid tumors underwent molecular profiling. Median time to assay results was 12 days. Results were contributive for 1658 patients (94%). At least one actionable target was detected in 1059 patients (64%) with a total of 1825 actionable alterations including alteration of the DNA damage repair response pathway (n = 336, 18%), high TMB (>16 mutations/Mb; n = 243, 13%), PIK3CA mutations (n = 150, 8%), ERBB family pathway alterations (n = 127, 7%), PTEN alterations (n = 95, 5%), FGFR alterations (n = 67, 4%) and MET activations (n = 13, 0.7%). The MTB recommended a matched therapy for 597 patients (56%) with a total of 819 therapeutic orientations: clinical trials (n = 639, 78%), off-label/compassionate use (n = 81, 10%), approved drug (n = 51, 6%), and early access program (n = 48, 6%). In total, 122 patients (21%) were treated. Among the assessable patients (n = 107), 4 (4%) had complete response, 35 (33%) had partial response, 27 (25%) had stable disease, and 41 (38%) a progressive disease as best response. The median progression-free survival and median overall survival were 4.7 months (95% confidence interval 2.7-6.7 months) and 8.3 months (95% confidence interval 4.7-11.9 months) respectively.CONCLUSIONS: ctDNA sequencing with a large panel is an efficient approach to match patients with advanced cancer with targeted therapies.
KW - Biomarkers, Tumor/genetics
KW - Circulating Tumor DNA/genetics
KW - DNA, Neoplasm/genetics
KW - High-Throughput Nucleotide Sequencing/methods
KW - Humans
KW - Mutation
KW - Neoplasms/drug therapy
KW - Precision Medicine/methods
KW - Prospective Studies
KW - targeted therapy
KW - ctDNA
KW - precision medicine
KW - ESCAT
UR - http://www.scopus.com/inward/record.url?scp=85149654853&partnerID=8YFLogxK
U2 - 10.1016/j.annonc.2023.01.008
DO - 10.1016/j.annonc.2023.01.008
M3 - Journal article
C2 - 36709039
SN - 0923-7534
VL - 34
SP - 389
EP - 396
JO - Annals of Oncology
JF - Annals of Oncology
IS - 4
ER -