Precision medicine trial highlights the need for a new approach in treating genomically complicated cancers

Date:
15 July 2020

A pioneering lung cancer study has highlighted important factors that will need to be considered in the next wave of precision medicine studies particularly in treating genomically complicated cancers.

Published in Nature, the National Lung Matrix Trial (NLMT) is the world’s largest precision medicine clinical trial for non-small-cell lung cancer (NSCLC) patients. The Royal Marsden NHS Foundation Trust played a crucial role in this trial, as a major recruiting site and one of three centres to carry out the molecular profiling.

Using an innovative trial design that incorporates multiple treatment arms, NLMT allows for a more flexible and informed approach than traditional clinical trials. Each arm tests a different targeted treatment matched to a different genetic subtype of NSCLC. 

The trial’s adaptive approach makes it possible for new drugs and combinations to be added as soon as they become available or retired quickly and easily if evidence suggests they aren’t effective.

Patients who sign up to take part in NLMT are genetically screened to understand more about their tumour type, and whether they possess the relevant genetic signatures to be matched to a targeted treatment. 

Since the trial opened to recruitment in May 2015 until November 2019, 288 patients have been recruited to the 19 targeted treatment cohorts on the trial.

Results revealed key learnings on the use of precision medicine, such as how the appropriate pre-clinical work is essential in defining appropriate biomarker-drug combinations to test in the clinic, on ensuring that the best drugs available are used to hit the genomic targets, the scale of attrition from large screening platforms, and the importance of analysing and publishing outcome data of an ongoing study.

The attrition rate was high with only a 5% of SMP2 patients receiving treatment on NLMT. As trials often come towards the end of the patient journey, cancer progression might make patients too unwell to be recruited onto trials.

Targeted therapy trials should take place much earlier in the cancer journey and use blood based genomic testing for fast turn-round of the information needed to match patients to drugs. 

Professor Sanjay Popat, Consultant Medical Oncologist at The Royal Marsden was lead investigator for patients receiving crizotinib and Chair of the trial management group. He described the trial findings as ‘important’ for lung cancer patients:

“For some patients in the trial we did see positive outcomes. It reconfirms our recommendations that we need to understand the individual molecular profile of patients and target those mutations with personalised treatment. 

 For some patients in the trial we did see positive outcomes. It reconfirms our recommendations that we need to understand the individual molecular profile of patients and target those mutations with personalised treatment. 

Professor Sanjay Popat, Consultant Medical Oncologist at The Royal Marsden

Professor Popat added that trials in lung cancer are particularly difficult, and not all patients benefited.

“Testing new drugs in lung cancer is a real challenge as it is an aggressive disease. Unfortunately for some patients they did not see a positive improvement. What we should now do is coordinate more research on a wider scale, using this as an opportunity to further expand our knowledge of targeting gene mutations.”

Next steps in the NLMT are to continue recruiting patients. A new combination arm has just been added to the study and opened earlier in June. There will also be further publications from the individual arms and cohorts, and translational laboratory work.

The trial was led by the University of Birmingham’s Cancer Research UK Clinical Trials Unit, funded by Cancer Research UK (CRUK) and supported by the charity’s Stratified Medicine Programme Phase 2 (SMP2) screening platform.

A £25 million collaboration with Pfizer, AstraZeneca and other pharmaceutical companies, and with support from the NHS, the NLMT matches different treatments to different groups of patients based on genetic changes in their cancer. 

Patient Story:

Graham, 59, was diagnosed in 2017 with lung cancer. After having chemotherapy and immunotherapy, his clinical team at The Royal Marsden recommended he went on to the Matrix trial. He takes the drug orally twice a day, and has had an amazing response.

"It was quite an instant impact,” he explains. “We saw a big reduction in the size of my primary tumour – around 59% within four months of starting the trial – and it’s maintained around that level since. I’ve had very minimal side effects, so have been able to get on with life and spending time with my family.”

During the COVID-19 pandemic Graham’s treatment continued, but clinical teams amended his schedule to minimise his attendance at hospital. He has had regular phone calls with them, and was able to have his drugs delivered to home.

Graham adds: “I have been shielding at home throughout the pandemic. It’s been reassuring to know that the team at The Royal Marsden is there if you need them”.