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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 ↗