New tests select patients who could live for nearly a year longer on targeted bowel cancer drug

Date:
09 August 2017

Giving patients with bowel cancer an MRI scan and a blood test could pick out those who would benefit from a targeted cancer treatment, a new study reports

Researchers found that after only two weeks on the drug regorafenib, a test based on an MRI scan could tell which patients would respond an average of 9.4 months longer than those whose treatment failed early.

Testing for cancer DNA in the bloodstream also tracked the benefit of treatment – with patients with low levels of cancer DNA after two months surviving an average of 9.7 months longer than those where there was no change or an increase.

Early findings suggest that combining the MRI scan with the blood test could give an even stronger prediction of which patients will respond to treatment.

The tests could allow doctors to rapidly identify which patients are no longer benefiting from treatment and switch them to an alternative drug.

A team at The Institute of Cancer Research and The Royal Marsden tested 27 patients with chemotherapy-resistant advanced bowel cancers and mutations in the gene KRAS, as part of a phase II clinical trial of regorafenib.

The new study is published today in the journal Gut, and was funded by Bayer Pharmaceuticals, Cancer Research UK, the NIHR Biomedical Research Centre at The Royal Marsden and The Institute of Cancer Research (ICR), and The Royal Marsden Cancer Charity.

How it works

One of the ways regorafenib works is by restricting the blood supply to tumours, starving them of oxygen and the vital nutrients they need to grow. The researchers developed a new method using MRI to assess whether the drug is hitting its target by viewing reductions in blood vessels feeding the tumour.

Patients who showed a reduction in tumour blood supply by 70% by an MRI all survived six months on the treatment, and 75% were still alive after a year. These patients survived for an average of 15.2 months, compared with only 5.8 months for those who didn’t respond to the drug in this way.

This is the first study to show in patients that regorafenib is effective because it restricts the blood supply to tumours, starving them of oxygen and nutrients. The researchers also found that patients who responded well to the drug had a marked drop in cancer DNA in the bloodstream, which continued throughout treatment.

Some 48% of the 27 patients in the trial sustained this drop in the level of circulating cancer DNA for two months. These patients survived 15.2 months after beginning treatment, compared with only 5.5 months for patients who experienced no change or an increase in the levels of circulating DNA.

Moving forward 

Early data on use of the two tests together has prompted optimism that they could be even more effective at picking out patients who are most likely to respond – guiding clinical decisions with greater confidence. Regorafenib is licensed for people with bowel cancer for whom all other chemotherapy options have failed, but it is not available on the NHS, in part because of doubts over its effectiveness in unselected patients.

Tests that quickly identify who could benefit from the treatment are urgently needed, since patients with bowel cancer that has spread around the body don’t have many effective treatment options open to them. A trial will now be run in a larger group of patients that assesses using both tests in succession.

Study leader Dr Nicola Valeri, Team Leader in Gastrointestinal Cancer Biology and Genomics at The Institute of Cancer Research, and a Consultant Medical Oncologist at The Royal Marsden, said: “We have developed new tests with the potential to detect very quickly which patients are likely to respond long term to the drug regorafenib – and that give an early warning of treatment failure in others who could be switched to another treatment.

"Bowel cancer that has spread around the body is a difficult disease to treat. Although a number of treatments are available they don’t always work in the long term, so it’s great that it seems we can now pick out patients for whom regorafenib could offer many extra months of life.

"We are now beginning a new trial to make sure that the tests work in a larger group of patients. If our findings are confirmed we hope policy makers will reconsider the recommendation against use of regorafenib on the NHS for people with bowel cancer. We could then use the tests in the clinic to benefit patients who badly need hard and fast answers on whether their treatment will give them precious extra time with their loved ones.”

Professor David Cunningham, Director of the NIHR Biomedical Research Centre at The Royal Marsden and The Institute of Cancer Research, who was Chief Investigator of the clinical trial associated with the study, said: “At The Royal Marsden targeted, precision medicine is at the very core of our work and we believe this is a very important test for patients with advanced bowel cancer. 

Being able to identify which patients benefit from regorafenib, and giving them an extra year with their loved ones, shows the importance of our research work for this particular group of patients who currently have limited options available to them.”