Patient-centric trials for therapeutic development in precision oncology

Abstract

Our increasing understanding of the molecular pathology of disease, particularly through genomic studies, has created significant opportunities for the development of therapeutics that specifically target discrete molecular subclasses, but equally, has generated substantial challenges in how to develop and implement these strategies. Variously termed personalised, stratified, individualised or precision medicine, the approach is centered on delivering the optimal therapy for an individual based on specific clinical and molecular features of their disease. The development of new therapeutics that target molecular mechanisms has driven considerable change and innovation in clinical trial strategies. We have made progress through improved efficiency and changes in clinical trial design, yet continued innovation through the modification of existing core paradigms in oncology drug development and clinical care are required to fully realise the promise of precision medicine.

The Therapeutic Potential of Targeting the HGF/cMET Axis in Ovarian Cancer

“…Such trials are most efficacious when they assess a potential therapeutic effect that is about the same size or slightly smaller than the effect of the natural variation that exists between individuals [70]. One of the surprising details to come out of recent trials using HGF or cMET targeting agents is the absence of patient selection using biomarkers, or indeed correlation of results post-hoc, with HGF/Met expression.…”

Challenges and methodology in the incorporation of biomarkers in cancer clinical trials

“…To ensure reproducibility, preclinical work should include a statement about the test's quality controls, what the assay is designed to measure, optimal assay conditions, the specific kit or critical reagents, details of the scoring system, selection of a uniform threshold for binary interpretation of results, a statement regarding the reproducibility or precision, sensitivity, specificity, and a reference to the clinical validation of the assay, such as comparing results using the same samples in different laboratories (50). As assays can change due to new platform availability and as new promising biomarkers can be discovered during the course of an ongoing trial, a flexible protocol should be adopted to incorporate emerging changes along with good specimen storage so that biopsies can be re-tested with the new assay and results compared to the old assay (52). Also as bioinformatics software and assay platform regularly change, it is important to specify the version used during the course of a clinical trial.…”

Genomic Heterogeneity: Next-Generation Sequencing Enables Biomarker Identification for Hepatocellular Carcinoma

“…The easy and low-cost conduction of targeted NGS on a panel of known genes can identify cancer driver genes involved in a specific (umbrella design) or multiple (basket design) cancer types [11]. Although there have been no umbrella and basket studies on HCC, highly promising findings have been reported for other cancer types [12,13].…”