Revisited analysis of a SHIVA01 trial cohort using functional mutational analyses successfully predicted treatment outcome

被引:3
作者
Kamal, Maud [1 ,2 ]
Tarcic, Gabi [3 ]
Dureau, Sylvain [4 ]
Edelheit, Oded [3 ]
Barbash, Zohar [3 ]
Lecerf, Charlotte [1 ,2 ]
Morel, Claire [1 ,2 ]
Miron, Benjamin [3 ]
Callens, Celine [5 ]
Servant, Nicolas [6 ]
Bieche, Ivan [5 ]
Vidne, Michael [3 ]
Le Tourneau, Christophe [1 ,2 ,6 ,7 ]
机构
[1] Inst Curie, Dept Drug Dev & Innovat, 35 Rue Dailly, F-92210 Paris, France
[2] Inst Curie, Dept Drug Dev & Innovat, St Cloud, France
[3] NovellusDx, Jerusalem, Israel
[4] Inst Curie, Dept Biostat, Paris, France
[5] Inst Curie, Dept Genet, Paris, France
[6] Inst Curie, INSERM U900, St Cloud, France
[7] Versailles St Quentin En Yvelines Univ, Montigny Le Bretonneux, France
关键词
drug response; in vitro functional assay; mutation; oncogenic activity; variant with unknown significance; ADVANCED CANCER;
D O I
10.1002/1878-0261.12180
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
It still remains to be demonstrated that using molecular profiling to guide therapy improves patient outcome in oncology. Classification of somatic variants is not straightforward, rendering treatment decisions based on variants with unknown significance (VUS) hard to implement. The oncogenic activity of VUS and mutations identified in 12 patients treated with molecularly targeted agents (MTAs) in the frame of SHIVA01 trial was assessed using Functional Annotation for Cancer Treatment (FACT). MTA response prediction was measured in vitro, blinded to the actual clinical trial results, and survival predictions according to FACT were correlated with the actual PFS of SHIVA01 patients. Patients with positive prediction had a median PFS of 5.8months versus 1.7months in patients with negative prediction (P<0.05). Our results highlight the role of the functional interpretation of molecular profiles to predict MTA response.
引用
收藏
页码:594 / 601
页数:8
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