Implementation and use of whole exome sequencing for metastatic solid cancer

Autor: Juliette Albuisson, Sylvain Ladoire, François Ghiringhelli, Julie Niogret, Christophe Borg, Pascal Foucher, Audrey Hennequin, Isabelle Desmoulins, Jean-Florian Guion Dusserre, Jean David Fumet, Thomas Collot, Julie Vincent, Laure Favier, Romain Boidot, Caroline Truntzer, Sophie Nambot, Côme Lepage, Laurence Faivre, Julie Blanc, Corentin Richard, Manon Réda, Aurélie Bertaut, Laurent Arnould, Alice Hervieu, Leila Bengrine
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Oncology
Adult
Male
medicine.medical_specialty
Research paper
medicine.medical_treatment
lcsh:Medicine
somatic and constitutional analysis
routine care
Systemic therapy
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
Young Adult
0302 clinical medicine
Internal medicine
Neoplasms
Exome Sequencing
medicine
Genetic predisposition
Clinical endpoint
Humans
Neoplasm Metastasis
Exome
metastatic cancer precision Medicine
Exome sequencing
Aged
Aged
80 and over
lcsh:R5-920
Molecular profiling of cancer
business.industry
lcsh:R
Cancer
General Medicine
Immunotherapy
exome sequencing analysis
Middle Aged
medicine.disease
Progression-Free Survival
Clinical trial
030104 developmental biology
Genetics
Population
030220 oncology & carcinogenesis
Mutation
Female
lcsh:Medicine (General)
business
Zdroj: EBioMedicine
EBioMedicine, Vol 51, Iss, Pp-(2020)
ISSN: 2352-3964
Popis: Background: Genomically-guided clinical trials are performed across different tumor types sharing genetic mutations, but trial organization remains complex. Here we address the feasibility and utility of routine somatic and constitutional exome analysis in metastatic cancer patients. Methods: Exoma trial (NCT02840604) is a multicenter, prospective clinical trial. Eligible patients presented a metastatic cancer progressing after at least one line of systemic therapy. Constitutional genetics testing required geneticist consultation. Somatic and germline exome analysis was restricted to 317 genes. Variants were classified and molecular tumor board made therapeutic recommendations based on ESMO guidelines. Primary endpoint was the feasibility of the approach evaluated by the proportion of patient that received a therapeutic proposal. Findings: Between May 2016 and October 2018, 506 patients were included. Median time required for tumor sample reception was 8 days. Median time from sample reception to results was 52 days. Somatic analysis was performed for 456 patients (90.1%). Both somatic and constitutional analyses were successfully performed for 386 patients (76.3%). In total, 342 patients (75%) received a therapeutic proposal. Genetic susceptibility to cancer was found in 35 (9%) patients. Only, 79 patients (23.1%) were treated with NGS matched therapy mainly PI3K/AKT/mTOR inhibitors 22 (27.8%), followed by PARP inhibitors 19 (24.1%), antiangiogenics 17 (21.5%), MEK inhibitors 7 (8.9%) and immunotherapy 5 (6.3%). Matched treatment was finally stopped because of disease progression 50 (63%), treatment toxicity 18 (23%), patients’ death 4 (5%). PFS2/PFS1 ratio was > 1,3 for 23,5% of patients treated with the NGS matched therapy and 23,7% of patients treated with standard therapy. Interpretation: Study shows that exome analysis is feasible in cancer routine care. This strategy improves detection of genetic predispositions and enhances access to target therapies. However, no differences were observed between PFS ratios of patients treated with matched therapy versus standard therapy. Funding: This work was funding by the centre Georges Francois Leclerc Keywords: Molecular profiling of cancer, exome sequencing analysis, somatic and constitutional analysis, routine care, metastatic cancer precision Medicine
Databáze: OpenAIRE
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