Genomic Features of Exceptional Response in Vemurafenib ± Cobimetinib-treated Patients with


Journal

Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500

Informations de publication

Date de publication:
01 06 2019
Historique:
received: 14 03 2018
revised: 01 11 2018
accepted: 22 02 2019
pubmed: 3 3 2019
medline: 7 7 2020
entrez: 3 3 2019
Statut: ppublish

Résumé

Previous investigations identified transcriptional signatures associated with innate resistance to anti-programmed cell death protein 1 therapy in melanoma. This analysis aimed to increase understanding of the role of baseline genetic features in the variability of response to BRAF and MEK inhibitor therapy for This exploratory analysis compared genomic features, using whole-exome and RNA sequencing, of baseline tumors from patients who had complete response versus rapid progression (disease progression at first postbaseline assessment) on treatment with cobimetinib combined with vemurafenib or vemurafenib alone. Associations of gene expression with progression-free survival or overall survival were assessed by Cox proportional hazards modeling. Whole-exome sequencing showed that These findings suggest that enriched immune infiltration might be a shared feature favoring response to both targeted and immune therapies, while features of innate resistance to targeted and immune therapies were distinct.

Identifiants

pubmed: 30824584
pii: 1078-0432.CCR-18-0720
doi: 10.1158/1078-0432.CCR-18-0720
pmc: PMC8083896
mid: NIHMS1692052
doi:

Substances chimiques

Azetidines 0
Biomarkers, Tumor 0
Piperidines 0
Vemurafenib 207SMY3FQT
BRAF protein, human EC 2.7.11.1
Proto-Oncogene Proteins B-raf EC 2.7.11.1
cobimetinib ER29L26N1X

Types de publication

Journal Article Multicenter Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

3239-3246

Subventions

Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States

Informations de copyright

©2019 American Association for Cancer Research.

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Auteurs

Yibing Yan (Y)

Genentech, Inc., South San Francisco, California.

Matthew J Wongchenko (MJ)

Genentech, Inc., South San Francisco, California.

Caroline Robert (C)

Institut Gustave Roussy, Villejuif, France.

James Larkin (J)

The Royal Marsden NHS Foundation Trust, The Royal Marsden Hospital, London, United Kingdom.

Paolo A Ascierto (PA)

Istituto Nazionale Tumori Fondazione Pascale, Napoli, Italy.

Brigitte Dréno (B)

Nantes University, CHU Nantes, France.

Michele Maio (M)

Center for Immuno-Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy.

Claus Garbe (C)

Universitätsklinikum Tübingen, Tübingen, Germany.

Paul B Chapman (PB)

Memorial Sloan Kettering Cancer Center, New York, New York.

Jeffrey A Sosman (JA)

Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois.

Zhen Shi (Z)

Genentech, Inc., South San Francisco, California.

Hartmut Koeppen (H)

Genentech, Inc., South San Francisco, California.

Jessie J Hsu (JJ)

Genentech, Inc., South San Francisco, California.

Ilsung Chang (I)

Genentech, Inc., South San Francisco, California.

Ivor Caro (I)

Genentech, Inc., South San Francisco, California.

Isabelle Rooney (I)

Genentech, Inc., South San Francisco, California.

Grant A McArthur (GA)

Peter MacCallum Cancer Centre, Melbourne, Australia and University of Melbourne, Parkville, Australia.

Antoni Ribas (A)

Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, David Geffen UCLA School of Medicine, Los Angeles, California. aribas@mednet.ucla.edu.

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Classifications MeSH