AREG, EREG and EGFR: response to anti-EGFR agents in colorectal cancer
Research type
Research Study
Full title
Association between tumour amphiregulin, epiregulin and epidermal growth factor receptor (EGFR) expression and response to anti-EGFR agents in colorectal cancer
IRAS ID
264745
Contact name
Jean Uniacke
Contact email
Sponsor organisation
University of Leeds
Clinicaltrials.gov Identifier
NCT03986541, clinicaltrials.gov
Duration of Study in the UK
3 years, 8 months, 0 days
Research summary
Research Summary:
Some bowel cancer cells have a chemical (protein) on their surface called EGFR. This chemical can make the cancer cells multiply. Drugs have been developed to block this chemical so that the cancer cells stop multiplying and some of them die. Unfortunately, these drugs don’t work for everyone with bowel cancer. This is a problem because the drugs have some unpleasant side effects and so some patients are suffering from side effects without getting any benefit.We want to develop a test to predict who will and will not get a benefit from these drugs before they are given. We know about two other chemicals that make EGFR work harder. We have done some work that suggests that people with high levels of these chemicals in their cancer are more likely to get a benefit from drugs against EGFR. In this study we want to check this on a larger scale to make sure this is a useful test.
We will be asking patients who have either had drugs against EGFR in the past or are about to start them if they are happy for us to look into whether or not they benefited from them. Patients will have had a biopsy of their cancer or may have had surgery to remove cancer in the past. The cancer will have been studied under the microscope and then put into storage. We will ask if we can use these stored samples to run our extra tests. We will then see if it is true that patients with high levels of the chemicals we are testing respond better to drugs against EGFR.
Funding for this project has been provided jointly by a public body and Roche, a company that develops drugs and tests. We aim to study 960 patients over 32 months.
Lay summary of study results:
Some bowel cancer cells have a chemical (protein) on their surface called EGFR. This chemical can make the cancer cells multiply. Drugs have been developed to block this chemical so that the cancer cells stop multiplying and some of them die. Unfortunately, these drugs don’t work for everyone with bowel cancer. This is a problem because the drugs have some unpleasant side effects and so some patients are suffering from side effects without getting any benefit.We wanted to develop a test to predict who does and does not get a benefit from these drugs before they are given. We know about two other chemicals that make EGFR work harder. We had previously done some work suggesting that people with high levels of these chemicals in their cancer are more likely to get a benefit from drugs against EGFR. In this study we wanted to check that this is true in a larger number of patients.
We recruited 541 patients who had previously received treatment with anti-EGFR drugs. We looked at how long their cancer had remained under control on these drugs. We also used stored samples of the patients' tumour samples to examine them for the two chemicals that make EGFR work harder. We found that patients with cancers that contained higher levels of these proteins were kept under control by the anti-EGFR drugs for longer than those with lower levels. We developed the test for this with the diagnostics company, Roche Diagnostics. We are now conducting a clinical trial to see if we can predict in advance which patients do well with anti-EGFR drugs. The results of our study were presented at an international conference (ASCO, Chicago, 2023) and in a medical journal (Clinical Cancer Research). We have also discussed the results with patients when planning the clinical trial that is now underway.
REC name
Yorkshire & The Humber - South Yorkshire Research Ethics Committee
REC reference
19/YH/0235
Date of REC Opinion
9 Aug 2019
REC opinion
Favourable Opinion