Colorectal cancer: Anti-EGFR treatment, systematic review and aggregate data meta-analysis
Does anti-EGFR therapy improve outcome in advanced colorectal cancer? A systematic review and meta-analysis
Does anti-EGFR treatment benefit people with advanced bowel cancer?
What was this study about?
For patients with tumours that have spread outside the bowel (advanced or metastatic bowel cancer) and for whom surgery to remove the tumour is not possible, treatments include chemotherapy (drug treatment) and or radiotherapy (treatment with x-rays) to help patients to live for longer.
Recently, a number of new treatments (sometimes called biological treatments or targeted treatments) have been used in clinical trials. These treatments are antibodies that attach to receptors (called epidermal growth factor receptors or EGFR) that are found on the surface of cancer cells. This blocks the receptor and stops the cancer cells from growing. However, some people with bowel cancer have genetic changes in their cancer cells, called "k-ras mutations". Some trials have suggested that the antibodies might not work for people with k-ras mutations.
In 2009, we started a new systematic review looking at the two anti-EGFR targeted treatments, cetuximab and panitumumab for people with advanced bowel cancer. This brought together information from the reports of similar trials. These trials compared what happened to people with advanced bowel cancer who were given anti-EGFR targeted treatments with standard care (either chemotherapy or best supportive care) with those who were given standard care alone. This study aimed to find out whether anti-EGFR targeted treatments helped people to live longer without the cancer from spreading. It also aimed to see:
- If anti-EGFR targeted treatments worked differently in people with k-ras mutations (compared with those with no mutations)
- Whether adding anti-EGFR targeted treatments to different chemotherapy drugs made any difference to how well it worked
- Whether giving anti-EGFR targeted treatments and other targeted treatments together with chemotherapy gave any more benefits
What difference did this study make?
This study showed that people with advanced bowel cancer with no k-ras gene changes and who had anti-EGFR targeted treatments plus best supportive care lived for almost 5 months without the cancer spreading, compared with around 2 months for people who had best supportive care alone. It was not clear whether anti-EGFR targeted treatments helped people to live longer overall.
For people with advanced bowel cancer with no k-ras gene changes and who had anti-EGFR targeted treatments plus chemotherapy that included the drug 5-fluorouracil (or 5-FU), the study showed they lived for 9.5 months without the cancer spreading, compared with around 7 months for people who had chemotherapy alone. It was less clear whether anti-EGFR targeted treatments helped people to live longer overall.
The study also showed that anti-EGFR targeted treatments did not help people with advanced bowel cancer with k-ras gene changes whether they had the anti-EGFR targeted treatments alongside best supportive care or chemotherapy. It also showed that it may be harmful to people with advanced bowel cancer if anti-EGFR targeted treatments are given with chemotherapy and bevacizumab, but the reasons for this are not clear.
Vale CL, Tierney JF, Fisher D, Adams RA, Kaplan R, Maughan TS, et al. Does anti-EGFR therapy improve outcome in advanced colorectal cancer? A systematic review and meta-analysis. Cancer Treatment Reviews. 2012;38(6):618-25
Type of study
Who funded the study?
The Medical Research Council
When did it take place?
This study was completed in December 2010.
Where did it take place?
The study was done at the MRC Clinical Trials Unit. It brought together the results of trials from all over the world.
Who was included?
Patients with advanced bowel cancer who took part in randomised controlled trials comparing either:
- Anti-EGFR targeted treatments plus best supportive care with best supportive care alone
- Anti-EGFR targeted treatments plus chemotherapy with chemotherapy alone
There were 14 trials that included more than 10,200 patients with advanced bowel cancer.