Heterogeneity in the tumour size dynamics differentiates Vemurafenib, Dabrafenib and Trametinib in metastatic melanoma

Hitesh Mistry, David Orrell, Raluca Eftimie

 

Abstract

Molecular heterogeneity in tumours leads to variability in drug response both between patients and across lesions within a patient. These sources of variability could be explored through analysis of routinely collected clinical trial imaging data. We applied a mathematical model of tumour growth to analyse both within and between patient variability in tumour size dynamics to clinical data from three drugs, Vemurafenib, Dabrafenib and Trametinib, used in the treatment of metastatic melanoma. 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. 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.

Keywords: heterogeneity, vemurafenib, dabrafenib, trametinib, melanoma, metastasis 

doi: http://biorxiv.org/content/early/2017/01/26/103366