- In this guidelines update for managing metastatic colorectal cancer ([m]CRC), the National Comprehensive Cancer Network (NCCN) adds major updates for BRAF-mutated advance cancers, approval of larotrectinib for broad tissue types, and more information regarding Lynch syndrome testing.
Why this matters
- These changes have been made in the last year for managing one of the most common cancers worldwide, with limited 5-year survival with mCRC.
- 4 consensus molecular subtypes (CMS 1 through 4) are characterized, associated with OS differences.
- Treatment options based on BRAF/MEK and NTRK fusion targets (e.g., tissue-agnostic approval for the NTRK inhibitor larotrectinib) have been added.
- Guidelines note that BRAF positivity does not rule out Lynch syndrome.
- Regarding Lynch syndrome, germline testing, mismatch repair (MMR) immunohistochemistry recommended with family history of cancer.
- mFOLFOXIRI + panitumumab added for unresectable stage IV mCRC, only for KRAS/NRAS/BRAF wild-type, left-sided tumors.
- Nivolumab±ipilimumab or pembrolizumab okayed for second-, third-line treatment of dMMR/microsatellite instability-H CRC.
- New second-line combination treatment options for BRAF-mutated CRC:
- Dabrafenib + trametinib + cetuximab or panitumumab.
- Encorafenib + binimetinib + cetuximab or panitumumab.