Clinical utility of circulating tumor DNA sequencing with a large panel: a National Center for Precision Medicine (PRISM) study

被引:33
作者
Bayle, A. [1 ,2 ,3 ]
Belcaid, L. [1 ,4 ]
Aldea, M. [5 ]
Vasseur, D. [6 ]
Peyraud, F. [7 ]
Nicotra, C. [1 ]
Geraud, A. [1 ]
Sakkal, M. [1 ,5 ]
Seknazi, L. [1 ]
Cerbone, L. [5 ]
Blanc-Durand, F. [5 ]
Hadoux, J. [5 ]
Mosele, F. [5 ]
Tagliamento, M. [5 ]
Bernard-Tessier, A. [2 ,5 ]
Verret, B. [2 ,5 ]
Smolenschi, C. [1 ]
Clodion, R. [1 ]
Auger, N. [6 ]
Romano, P. M. [1 ]
Gazzah, A. [1 ]
Camus, M. N. [1 ]
Micol, J. [8 ]
Caron, O. [9 ]
Hollebecque, A. [1 ]
Loriot, Y. [1 ]
Besse, B. [2 ,5 ]
Lacroix, L. [6 ]
Rouleau, E. [6 ]
Ponce, S. [8 ]
Soria, J. C. [2 ,5 ]
Barlesi, F. [2 ,5 ]
Andre, F. [2 ,5 ]
Italiano, A. [1 ,7 ,10 ,11 ]
机构
[1] Drug Dev Dept DITEP Gustave Roussy, Canc Campus, Villejuif, France
[2] Univ Paris Saclay, Fac Med, Gif Sur Yvette, France
[3] Paris Saclay Univ, Oncostat U1018, Inserm, Labeled Ligue Canc, Villejuif, France
[4] Univ Copenhagen, Dept Oncol, Rigshospitalet, Copenhagen, Denmark
[5] Gustave Roussy, Dept Canc Med, Villejuif, France
[6] Gustave Roussy, Dept Med Biol & Pathol, Villejuif, France
[7] Inst Bergonie Comprehens Canc Ctr, Dept Early Phase Trial Unit, Bordeaux, France
[8] Gustave Roussy, Dept Hematol, Villejuif, France
[9] Gustave Roussy, Dept Genet, Villejuif, France
[10] Univ Bordeaux, Fac Med, Bordeaux, France
[11] Dev Dept DITEP Gustave Roussy, Canc Cam,114 Rue Edouard Vaillant, F-94805 Vil, France
关键词
ctDNA; targeted therapy; ESCAT; precision medicine; GENETIC-HETEROGENEITY; LIQUID BIOPSY; THERAPY;
D O I
10.1016/j.annonc.2023.01.008
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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%), ER88 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 (20%) 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.
引用
收藏
页码:389 / 396
页数:8
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