PREDICTION OF RESPONSE TO REGORAFENIB

Administering a magnetic resonance imaging (MRI) scan and a blood test to patients with metastatic colorectal cancer may help to select those who would benefit from a targeted cancer treatment, a new study published by Khan et al in Gutreported.

Researchers found that after only 2 weeks on the drug regorafenib (Stivarga), 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 2 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 treatment plan.

Monitoring the Tumor Blood Supply

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

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

Patients who showed a reduction in tumor blood supply by 70% as viewable by MRI all survived 6 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.

Monitoring ctDNA in the Bloodstream

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.

About 48% of the 27 patients in the trial sustained this drop in the level of circulating tumor DNA (ctDNA) for 2 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 ctDNA.

Combining Testing Strategies

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.

A trial will now be run in a larger group of patients that assesses using both tests in succession.

The study was funded by Bayer Pharmaceuticals, Cancer Research UK, the NIHR Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and the ICR, and The Royal Marsden Cancer Charity.