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 - Romano, P. M.
AU - Gazzah, A.
AU - Camus, M. N.
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 - Publisher Copyright:
© 2023 European Society for Medical Oncology
PY - 2023/4/1
Y1 - 2023/4/1
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 - ESCAT
KW - ctDNA
KW - precision medicine
KW - targeted therapy
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 - Article
C2 - 36709039
AN - SCOPUS:85149654853
SN - 0923-7534
VL - 34
SP - 389
EP - 396
JO - Annals of Oncology
JF - Annals of Oncology
IS - 4
ER -