Perspectives on Treatment of Metastatic CRC - Episode 4

Use of Regorafenib in Refractory mCRC

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Along the continuum of care for patients with unresectable metastatic colorectal cancer (mCRC), the patient may go through several lines of treatment. The number varies depending on many factors, including the molecular profile of the tumor. For example, in a patient with a RAS wild-type tumor, treatment may begin with FOLFOX/bevacizumab and then proceed to FOLFIRI plus bevacizumab, aflibercept, or ramucirumab at progression. If the third-line choice is an anti-EGFR antibody and the patient’s disease continues to progress, regorafenib is a viable treatment option, Fakih states.

Regorafenib was approved based on the CORRECT clinical trial, conducted in patients who progressed on or were intolerant to all systemic chemotherapies and to anti-EGFR therapy in the setting of KRAS wild-type mCRC. Compared with placebo, regorafenib improved overall survival by 23%. The CORRECT trial enrolled patients with ECOG performance status (PS) of 0 or 1.

For younger patients and those with good PS, the 160-mg starting dose that was used in the trial is appropriate. However, for older patients, at starting dose of 120 mg should be considered, which can be escalated in cycle 2 if the patient tolerates the drug well, Fakih suggests. Toxicities should be carefully monitored during the first cycle, specifically within the first week of therapy.

Data presented from the CONCUR trial during the 2014 ESMO meeting showed a 45% improvement in overall survival with regorafenib versus placebo in Asian patients with mCRC that progressed after standard therapies. Notably, overall survival in this highly refractory group of patients was 8.8 months. Unlike the larger CORRECT trial, the CONCUR study did not require participants to have received previous therapy with bevacizumab.

While it is unclear why the results were better in Asian versus North American and European patients, one theory involved the absence of bevacizumab in a subgroup of patients. Overall survival was better in the group that had not received any targeted therapy. Nonetheless, the results confirm that for patients in whom everything else has failed, there is an improvement in overall survival associated with the use of regorafenib, Fakih states.