Colorectal cancer: guideline history

Anchored to: FDA approvals of encorafenib with cetuximab (April 2020, BEACON) and first-line pembrolizumab for MSI-high disease (June 2020, KEYNOTE-177)

• addedMetastatic, BRAF V600E, after first line: Encorafenib plus cetuximab (with or without binimetinib) after prior therapy.
• recategorisedMetastatic, MSI-high / dMMR, first line: Pembrolizumab moves from later lines to preferred first-line therapy.second line and beyond (accelerated approval 2017) → first line, preferred (category 1)

Anchored to: Annals of Oncology publication, January 2023

• addedMetastatic, HER2-amplified, RAS wild-type: Trastuzumab with tucatinib or lapatinib or pertuzumab recommended after chemotherapy for HER2-amplified RAS wild-type disease.
• recategorisedMetastatic, left-sided RAS/BRAF wild-type, first line: Anti-EGFR antibody with doublet chemotherapy stated as the preferred first-line option for left-sided RAS and BRAF wild-type tumours.option alongside bevacizumab → preferred [I, A]

Anchored to: FDA approvals of trifluridine/tipiracil with bevacizumab (August 2023, SUNLIGHT) and fruquintinib (November 2023, FRESCO-2)

• recategorisedMetastatic, third line and beyond: Trifluridine/tipiracil is now given with bevacizumab rather than alone.trifluridine/tipiracil monotherapy → trifluridine/tipiracil plus bevacizumab (category 1)
• addedMetastatic, third line and beyond: Fruquintinib after fluoropyrimidine, oxaliplatin, irinotecan, anti-VEGF and, where indicated, anti-EGFR therapy.

Anchored to: FDA approvals of adagrasib with cetuximab (June 2024), encorafenib with cetuximab and mFOLFOX6 in the first line (December 2024, BREAKWATER), sotorasib with panitumumab (January 2025, CodeBreaK 300) and nivolumab with ipilimumab for MSI-high disease (April 2025, CheckMate 8HW)

• addedMetastatic, KRAS G12C, after first line: Sotorasib plus panitumumab or adagrasib plus cetuximab after chemotherapy.
• recategorisedMetastatic, BRAF V600E, first line: Encorafenib plus cetuximab moves into the first line with mFOLFOX6.after first-line chemotherapy → first line with mFOLFOX6 (BREAKWATER)
• addedMetastatic, MSI-high / dMMR, first line: Nivolumab plus ipilimumab as a preferred first-line option.