Background
Lung cancer is a devastating and very common healthcare problem. It is the third most common cancer in the UK with 46,403 new cases in 2014 (Cancer Research UK Cancer Statistics website). It is also the most common cause of cancer death worldwide with 1.59 million deaths in 2012.
There has been a revolution in the management of NSCLC over the past 10 years. The discovery of the molecular basis of response to Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitors (TKIs) resulted in a paradigm shift in our thinking about this disease, from one dominated by nihilism driven by the experience of the limited activity of toxic chemotherapies to one based on the rational selection of personalised therapy based on the determination of actionable genetic changes.
In 2011 Cancer Research UK (CRUK) set up the Stratified Medicine Programme (SMP). The first part of the programme (SMP1) was aimed at proving the feasibility of implementing large scale molecular testing in cancer within the NHS, whilst obtaining consent from patients to use their molecular and routine clinical data for research.
It is obvious that the greater the number of patients screened, the greater the subsequent number of potential participants for trials of inhibitors in small, but important, actionable subsets, and for trials of therapies to evade the multiple mechanisms of resistance of standard of care targeted therapies. This is the simple founding principle of the National Lung Matrix Trial aligned to CRUK’s SMP2. This initiative aims to provide large volume national molecular pre-screening integrated with a national network to deliver a stratified clinical trial. It builds on the highly successful SMP1 which included 2036 lung cancer patients over two years. SMP2 is only the third truly national screening programme.
About the trial
The National Lung Matrix Trial is an ambitious adaptive programme which seeks to increase the number of actionable genetic abnormalities in non-small cell lung cancer. The trial essentially designates the umbrella structure under which multiple individual trial arms sit. Each arm is non-randomised with treatment allocated according to molecular genotype as determined by molecular pre-screening through SMP2. There is no standard control arm.
A key feature includes an optional repeat biopsy at progression for ascertainment of resistance mechanisms and collection of appropriate samples prior to therapy with the targeted agent to reveal potential positive and negative predictive biomarkers for that agent. The study will open at all ECMCs and other UK sites, under a single clinical trial protocol and regulatory submission.