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Two recent biomarker analyses that focused on the role of RAS
mutations in metastatic colorectal cancer (mCRC) are beneficial but not immediately practice changing, suggests Tanios Bekaii-Saab, MD. The largest of these studies was the phase III PRIME study that explored panitumumab plus FOLFOX as a first-line treatment for patients with mCRC. This trial found a higher survival benefit in patients with wild-type RAS
mutation treated with the EGFR inhibitor.
The second analysis was the phase II PEAK study, which examined KRAS
mutations. In this trial, FOLFOX6 plus panitumumab or bevacizumab was examined as a first-line treatment in patients with wild-type KRAS
mutant CRC. These results were similar to the PRIME study, demonstrating an improvement in survival for patients with wild-type RAS
mutant CRC treated with panitumumab.
These trials provide some insight into the role of certain RAS
mutations in patients with CRC; however, their full impact is dulled by the administration of FOLFOX rather than FOLFIRI, believes Bekaii-Saab. Recent studies have demonstrated an apparent synergistic relationship between EGFR inhibitors and irinotecan. As a result of these findings, none of the panelists recommend the administration of oxaliplatin with an EGFR inhibitor in favor of irinotecan. Despite this, in the near future, Bekaii-Saab believes that an expanded definition of mutations will be utilized to select EGFR inhibitors in CRC, expanding the current definition to include KRAS
, and possibly HRAS
In current guidelines, all patients should be tested for KRAS
upfront, even if an EGFR inhibitor is not the planned treatment, explains Fadi Braiteh, MD, CPI. Additionally, since KRAS
mutations occur early in the process, a rebiopsy may not be needed. Furthermore, Braiteh notes, a reporting method that directly communicates mutational analysis results into an electronic health record is in development.