Global Perspectives on Treatment of Metastatic Colorectal Cancer - Episode 1
Colorectal cancer (CRC) is a heterogeneous disease, which may result in different clinical presentations and varied therapeutic responses, states Fortunato Ciardiello, MD, PhD. However, novel laboratory techniques have revealed comprehensive information about gene alterations and gene expression profiles that are involved, leading to some therapeutics clues.
Tumors with mismatch repair deficiency are hypermutated and may be associated with higher neoantigen burden, Ciardiello notes. For these tumors, there may be a role for immunotherapy. Other mutations, such as those in RAS, are indicative of benefit from targeted therapy. In the metastatic setting, BRAF mutations may be among the worst prognostic factors. Overall, it remains uncertain how to translate this information into selecting the best specific therapies for individual patients, notes Ciardiello.
The most essential genetic test for metastatic CRC is RAS mutation testing, says Ciardiello. It is now understood that 50% to 60% of metastatic CRC harbors a mutation in either KRAS or NRAS. These mutations help select patients who do not benefit from anti-EGFR treatment.
Testing is fairly standard for all patients with metastatic disease before beginning treatment, comments Dirk Arnold, MD. It is vital to have information regarding gene mutations before determining treatment because effectiveness of anti-EGFR treatment requires RAS wild-type disease.