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
