Actionable Molecular Testing in CRC

A patient with refractory unresectable colorectal cancer (CRC) that is KRAS-positive can often progress quickly despite having an excellent performance status, says Fadi Braiteh, MD. There is currently a lack of data to support retreating this patient with cytotoxic agents, notes Braiteh, especially if the they have already received two lines of antiangiogenic agents.

Biopsies obtained just three years ago were examined using an initial polymerase chain reaction (PCR) analysis, to detect KRAS mutations. Today, next-generation sequencing is used widely to reveal the mutation status of the tumor and various other markers, such as microsatellite stability.

Clinicians are not likely to find another actionable mutation other than KRAS on current molecular profiles, comments Howard S. Hochster, MD, adding that CRC treatments are not available for other mutations, such as adenomatous polyposis coli and PI3K.

Clinicians prefer to use molecular profiles to help guide patients to phase I clinical trials, says Hochster. However, many of the reports generated by the companies conducting the tests have incomplete data. It is important for oncologists to increase their understanding about genetics and to avoid wasting resources on testing for mutations that are not actionable, notes Braiteh.