Study aid only. Verify against current guidelines, primary literature, staging manuals, and prescribing information before clinical use.

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Metastatic Colorectal Cancer — Systemic Therapy

First-line Second-line Later-line SECOND-LINE THIRD-LINE / LATER Metastatic colorectal cancer by biomarker dMMR / MSI-high RAS/BRAF-wt · left RAS-mut or right-sided BRAF V600E HER2-amplified KRAS G12C Later-line (agnostic) IO Pembrolizumab KEYNOTE-177 ↗ Dual-IO Nivolumab ± ipilimumab CheckMate 8HW ↗ Anti-EGFR FOLFOX/FOLFIRI + cetuximab/panitumumab CRYSTAL ↗ Anti-VEGF FOLFOX/FOLFIRI + bevacizumab first-line ↗ Targeted Encorafenib + cetuximab BEACON ↗ Dual anti-HER2 Tucatinib + trastuzumab MOUNTAINEER ↗ ADC Trastuzumab deruxtecan DESTINY-CRC02 ↗ Targeted Sotorasib + panitumumab CodeBreaK 300 ↗ Targeted Adagrasib + cetuximab KRYSTAL-1 ↗ TKI Regorafenib CORRECT ↗ Cytotoxic Trifluridine/tipiracil ± bev SUNLIGHT ↗ TKI Fruquintinib FRESCO-2 ↗