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Model based analysis of the heterogeneity in the tumour size dynamics differentiates vemurafenib, dabrafenib and trametinib in metastatic melanoma

PURPOSE: Explore the heterogeneity in dynamics of tumour response to vemurafenib, dabrafenib and trametinib using routinely collected clinical trial imaging data. METHODS: Time-series imaging data from the phase III studies of vemurafenib, dabrafenib and trametinib were collected through a data repo...

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Autores principales: Mistry, Hitesh B., Orrell, David, Eftimie, Raluca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778167/
https://www.ncbi.nlm.nih.gov/pubmed/29222604
http://dx.doi.org/10.1007/s00280-017-3486-3
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author Mistry, Hitesh B.
Orrell, David
Eftimie, Raluca
author_facet Mistry, Hitesh B.
Orrell, David
Eftimie, Raluca
author_sort Mistry, Hitesh B.
collection PubMed
description PURPOSE: Explore the heterogeneity in dynamics of tumour response to vemurafenib, dabrafenib and trametinib using routinely collected clinical trial imaging data. METHODS: Time-series imaging data from the phase III studies of vemurafenib, dabrafenib and trametinib were collected through a data repository. A mathematical model based on basic mechanisms of tumour growth was placed within a statistical modelling framework to analyse the data. RESULTS: The analysis revealed: (1) existence of homogeneity in drug response and resistance development within a patient; (2) tumour shrinkage rate does not relate to rate of resistance development; (3) vemurafenib and dabrafenib, two BRAF inhibitors, have different variability in tumour shrinkage rates. CONCLUSIONS: Overall these results show how analysis of the dynamics of individual lesions can shed light on the within and between patient differences in tumour shrinkage and resistance rates, which could be used to gain a macroscopic understanding of tumour heterogeneity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00280-017-3486-3) contains supplementary material, which is available to authorized users.
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spelling pubmed-57781672018-02-01 Model based analysis of the heterogeneity in the tumour size dynamics differentiates vemurafenib, dabrafenib and trametinib in metastatic melanoma Mistry, Hitesh B. Orrell, David Eftimie, Raluca Cancer Chemother Pharmacol Original Article PURPOSE: Explore the heterogeneity in dynamics of tumour response to vemurafenib, dabrafenib and trametinib using routinely collected clinical trial imaging data. METHODS: Time-series imaging data from the phase III studies of vemurafenib, dabrafenib and trametinib were collected through a data repository. A mathematical model based on basic mechanisms of tumour growth was placed within a statistical modelling framework to analyse the data. RESULTS: The analysis revealed: (1) existence of homogeneity in drug response and resistance development within a patient; (2) tumour shrinkage rate does not relate to rate of resistance development; (3) vemurafenib and dabrafenib, two BRAF inhibitors, have different variability in tumour shrinkage rates. CONCLUSIONS: Overall these results show how analysis of the dynamics of individual lesions can shed light on the within and between patient differences in tumour shrinkage and resistance rates, which could be used to gain a macroscopic understanding of tumour heterogeneity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00280-017-3486-3) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2017-12-08 2018 /pmc/articles/PMC5778167/ /pubmed/29222604 http://dx.doi.org/10.1007/s00280-017-3486-3 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Article
Mistry, Hitesh B.
Orrell, David
Eftimie, Raluca
Model based analysis of the heterogeneity in the tumour size dynamics differentiates vemurafenib, dabrafenib and trametinib in metastatic melanoma
title Model based analysis of the heterogeneity in the tumour size dynamics differentiates vemurafenib, dabrafenib and trametinib in metastatic melanoma
title_full Model based analysis of the heterogeneity in the tumour size dynamics differentiates vemurafenib, dabrafenib and trametinib in metastatic melanoma
title_fullStr Model based analysis of the heterogeneity in the tumour size dynamics differentiates vemurafenib, dabrafenib and trametinib in metastatic melanoma
title_full_unstemmed Model based analysis of the heterogeneity in the tumour size dynamics differentiates vemurafenib, dabrafenib and trametinib in metastatic melanoma
title_short Model based analysis of the heterogeneity in the tumour size dynamics differentiates vemurafenib, dabrafenib and trametinib in metastatic melanoma
title_sort model based analysis of the heterogeneity in the tumour size dynamics differentiates vemurafenib, dabrafenib and trametinib in metastatic melanoma
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778167/
https://www.ncbi.nlm.nih.gov/pubmed/29222604
http://dx.doi.org/10.1007/s00280-017-3486-3
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