Abstract
BACKGROUND: Randomised phase III clinical trials represent a methodological milestone to select effective drugs against metastatic cancers. In this context, and particularly in the efficacy assessment of biologic drugs, the initial metastatic tumour burden is a strong prognostic factor. METHODS: A systematic literature review of randomised, phase III, first-line, clinical trials in metastatic breast, colorectal, and lung cancers, published from 2016 to 2021, was performed. Three groups of variables were collected: identity-, method- (including tumour burden assessment) and outcome-related. RESULTS: Seventy trials were selected. A large portion of studies (41.4%) focused on the effects of biologic agents (signal inhibitors and immuno-therapies). A definition of low-burden disease based predominantly on the number of involved organs was reported in 28.6% of studies. No explicit reference to oligo-metastatic disease was found either in inclusion/exclusion criteria or in final descriptive data analyses. Disease extent, heterogeneously defined, was a stratification factor for randomisation in only 25.7% of studies. In two studies, a significant imbalance between arms in patients with low-burden disease was revealed. CONCLUSIONS: Attention to initial tumour burden in designing future clinical trials (including the harmonisation of definitions and the reporting of eventual oligo-metastatic disease, complete estimates of tumour volume, and its consideration as a stratification factor) should be increased.