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Tarabay, Anthony; Michot, Jean-Marie; Aupérin, Anne; Lazarovici, Julien; Rossignol, Julien; Ghez, David; Dartigues-Cuillères, Peggy; Vergé, Veronique; Ribrag, Vincent; Massard, Christophe; Camara-clayette, Valérie
Blood, 11/2019, Volume: 134, Issue: Supplement_1Journal Article
Patient's selection in early phase clinical trials is guided by stringent clinical criteria and can be supported or improved by precise tumor characterization and/or molecular stratification. Most of the precision medicine data are generated using historical tumor biopsies often collected before anticancer drugs treatment, which may thus only partially reflect the tumor's molecular landscape at inclusion in early phase clinical trials. The gold standard fresh tumor biopsy is not always feasible without risk for the patient. For this reason, ctDNA could be a simple, safe and attractive technique for obtaining critical information on the tumor genomic landscape. This study was designed to explore if whether NGS results obtained with from ctDNA could replace fresh tumor biopsies in patients (pts) at inclusion in early phase clinical trials. Data generated on both tissue samples collected in a short period of time in 52 pts treated for a B-cell aggressive lymphoma in the DITEP department at Gustave Roussy prior to inclusion were compared (18/52 pts had one course of chemotherapy between the 2 tissue samples). Characteristics at sampling were: mean age = 66 y.o., male/female: 32/20, Ann Arbor staging: 1/2/3/4 = 4 (7.7%), 5 (9.6%), 8 (15.4%) and 35 (67.3%) pts. The median number of prior chemotherapy was 2 (Min=1; Max=7). NGS tests were done using a panel of 39 genes and more recently 44 genes. 34 genes were found mutated in at least one pt. 150 mutations of pathologic significance were identified and 105 mutations out of 150 (70.0%) were concordant between the fresh biopsy and the blood (95%CI=62.0%; 77.2%). No patient had a mutation detected in the ctDNA analysis that was not found in the fresh tumor biopsy. In 8/52(15%) patients, no mutation was detected in both tumor biopsy and blood. Of the 44-remaining pts, 10 had no mutation detected in the blood and 34 pts (77.3%) carried at least one mutation detectable in both the tumor and blood. In 25/44patients (56.8%) all mutations identified in the tumor could be also detected in the blood (95%CI=41.0%; 71.7%), which are “informative ctDNA patients” if we consider that tumor biopsy is the “gold standard” as it is in clinical trials. Among the 44 pts that have at least one mutation detected in the tumor, the median VAF detection in the tumor biopsy was 41% (range 2-98%) and in the blood it was 7% (range 0-83%), but if we focus on the 105 mutations detected in both the biopsy and in the blood, the median VAF observed is 43% in the tumor (range 2-98%) and 14% in the blood (range 1-83%). Our results suggest that 85% of the pts included in phase I trials have at least one detectable mutation in the tumor biopsy, but approximately 50% of the pts have concordant mutations found in both ctDNA and fresh tumor samples. These results also suggest that ctDNA could be a useful tool in those “informative ctDNA” pts for residual disease assessment without sequential biopsies. Ribrag:MSD: Membership on an entity's Board of Directors or advisory committees; Nanostring: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Infinity: Membership on an entity's Board of Directors or advisory committees; Roche: Other: Travel, accommodations, and expenses ; BMS: Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, and expenses ; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; AZ: Membership on an entity's Board of Directors or advisory committees; ArgenX: Research Funding; Epizyme: Consultancy, Research Funding.
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