Early change in tumour size predicts overall survival in patients with first-line metastatic breast cancer.
Eur J Cancer
; 66: 95-103, 2016 10.
Article
en En
| MEDLINE
| ID: mdl-27544929
ABSTRACT
PURPOSE:
Clinical trials using change in tumour size (CTS) as a primary end-point benefit from earlier evaluation of treatment effect and increased study power over progression-free survival, ultimately resulting in more timely regulatory approvals for cancer patients. In this work, a modelling framework was established to further characterise the relationship between CTS and overall survival (OS) in first-line metastatic breast cancer (mBC).METHODS:
Data from three randomised phase III trials designed to evaluate the clinical benefit of gemcitabine combination therapy in mBC patients were collated. Two drug-dependent models were developed to describe tumour growth dynamics the first for paclitaxel/gemcitabine treatment and the second for docetaxel/gemcitabine treatment. A parametric survival model was used to characterise survival as a function of CTS and baseline patient demographics.RESULTS:
While the paclitaxel/gemcitabine model incorporated tumour shrinkage by both paclitaxel and gemcitabine with resistance to paclitaxel, the docetaxel/gemcitabine model incorporated shrinkage and resistance to docetaxel alone. Predictors for OS were CTS at week 8, baseline tumour size and ECOG performance status. Model predictions reveal that for an asymptomatic mBC patient with a 6-cm tumour burden, first-line paclitaxel/gemcitabine treatment offers a median OS of 28.6 months, compared to 26.0 months for paclitaxel alone.CONCLUSION:
A modelling framework was established, quantitatively describing the tumour growth inhibitory effects of various gemcitabine combotherapies and the effect of the resulting CTS on survival in first-line mBC. This work further supports the use of early CTS as a go/no-go decision point during phase II clinical evaluation of treatments for mBC.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
/
Protocolos de Quimioterapia Combinada Antineoplásica
Tipo de estudio:
Clinical_trials
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
Eur J Cancer
Año:
2016
Tipo del documento:
Article