Combined Transcriptome and Circulating Tumor DNA Longitudinal Biomarker Analysis Associates With Clinical Outcomes in Advanced Solid Tumors Treated With Pembrolizumab
Hernando-Calvo, Alberto (Universitat Autònoma de Barcelona. Departament de Medicina)
Cindy Yang, S.Y. (Princess Margaret Cancer Centre (Toronto, Canadà))
Vila-Casadesús, Maria (Vall d'Hebron Institut d'Oncologia)
Han, Ming (Princess Margaret Cancer Centre (Toronto, Canadà))
Amy Liu, Zhihui (Princess Margaret Cancer Centre (Toronto, Canadà))
Berman, A Hal K. (Princess Margaret Cancer Centre (Toronto, Canadà))
Spreafico, Anna (Princess Margaret Cancer Centre (Toronto, Canadà))
Razak, Albiruni Abdul (Princess Margaret Cancer Centre (Toronto, Canadà))
Lheureux, Stephanie (Princess Margaret Cancer Centre (Toronto, Canadà))
Hansen, Aaron R. (Princess Margaret Cancer Centre (Toronto, Canadà))
Lo Giacco, Deborah (Vall d'Hebron Institut d'Oncologia)
Abbas-Aghababazadeh, Farnoosh (Princess Margaret Cancer Centre (Toronto, Canadà))
Matito, Judit (Vall d'Hebron Institut d'Oncologia)
Haibe-Kains, Benjamin (Princess Margaret Cancer Centre (Toronto, Canadà))
Pugh, Trevor (Princess Margaret Cancer Centre (Toronto, Canadà))
Bratman, Scott V. (Princess Margaret Cancer Centre (Toronto, Canadà))
Aleshin, Alexey (Natera, Austin, TX)
Berche, Roger (Vall d'Hebron Institut d'Oncologia)
Saavedra, Omar (Vall d'Hebron Institut d'Oncologia)
Garralda, Elena (Vall d'Hebron Institut d'Oncologia)
Elston, Sawako (Princess Margaret Cancer Centre (Toronto, Canadà))
Siu, Lilian L. (Princess Margaret Cancer Centre (Toronto, Canadà))
Ohashi, Pamela S. (Princess Margaret Cancer Centre (Toronto, Canadà))
Vivancos, Ana (Vall d'Hebron Institut d'Oncologia)
Bedard, Philippe L (Princess Margaret Cancer Centre (Toronto, Canadà))

Data:	2024
Resum:	PURPOSE Immune gene expression signatures are emerging as potential biomarkers for immunotherapy (IO). VIGex is a 12-gene expression classifier developed in both nCounter (Nanostring) and RNA sequencing (RNA-seq) assays and analytically validated across laboratories. VIGex classifies tumor samples into hot, intermediate-cold (I-Cold), and cold subgroups. VIGex-Hot has been associated with better IO treatment outcomes. Here, we investigated the performance of VIGex and other IO biomarkers in an independent data set of patients treated with pembrolizumab in the INSPIRE phase II clinical trial (ClinicalTrials. gov identifier: NCT02644369). MATERIALS AND METHODS Patients with advanced solid tumors were treated with pembrolizumab 200 mg IV once every 3 weeks. Tumor RNA-seq data from baseline tumor samples were classified by the VIGex algorithm. Circulating tumor DNA (ctDNA) was measured at baseline and start of cycle 3 using the bespoke Signatera assay. VIGex-Hot was compared with VIGex I-Cold 1 Cold and four groups were defined on the basis of the combination of VIGex subgroups and the change in ctDNA at cycle 3 from baseline (DctDNA). RESULTS Seventy-six patients were enrolled, including 16 ovarian, 12 breast, 12 head and neck cancers, 10 melanoma, and 26 other tumor types. Objective response rate was 24% in VIGex-Hot and 10% in I-Cold/Cold. VIGex-Hot subgroup was associated with higher overall survival (OS) and progression-free survival (PFS) when included in a multivariable model adjusted for tumor type, tumor mutation burden, and PD-L1 immunohistochemistry. The addition of DctDNA improved the predictive performance of the baseline VIGex classification for both OS and PFS. CONCLUSION Our data indicate that the addition of DctDNA to baseline VIGex may refine prediction for IO.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	JCO Precision Oncology, Vol. 8 (August 2024) , ISSN 2473-4284

DOI: 10.1200/PO.24.00100
PMID: 39178369

12 p, 1.1 MB

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