## First-Line Chemotherapy for Metastatic CRC **Key Point:** FOLFOX + Bevacizumab is the preferred first-line regimen for fit patients with metastatic colorectal carcinoma, particularly when KRAS is wild-type and microsatellite status is stable [cite:Harrison 21e Ch 297]. ### Treatment Algorithm for mCRC ```mermaid flowchart TD A[Metastatic CRC, fit patient]:::outcome --> B{KRAS status?}:::decision B -->|Wild-type| C{MSI-H/dMMR?}:::decision B -->|Mutant| D[FOLFOX + Bevacizumab]:::action C -->|Yes| E[Nivolumab or Pembrolizumab]:::action C -->|No| F[FOLFOX + Bevacizumab]:::action D --> G[Assess response at 8 weeks]:::action F --> G E --> G ``` **High-Yield:** Bevacizumab (anti-VEGF monoclonal antibody) improves overall survival and progression-free survival when added to chemotherapy in mCRC. The combination is superior to chemotherapy alone [cite:Robbins 10e Ch 17]. ### Chemotherapy Options in mCRC | Regimen | Components | Indication | Notes | |---------|-----------|-----------|-------| | **FOLFOX + Bevacizumab** | 5-FU/LV + Oxaliplatin + Anti-VEGF | First-line (KRAS WT, MSS) | Standard of care | | FOLFIRI + Bevacizumab | 5-FU/LV + Irinotecan + Anti-VEGF | Second-line or if oxaliplatin contraindicated | Alternative backbone | | FOLFOX/FOLFIRI + Cetuximab | Chemotherapy + Anti-EGFR | KRAS WT, RAS WT only | Inferior to bevacizumab in some trials | | Regorafenib | Multikinase inhibitor | Third-line (after 2 prior regimens) | Salvage therapy | | Nivolumab/Pembrolizumab | PD-1 inhibitors | MSI-H/dMMR tumors | Not for MSS disease | **Clinical Pearl:** Bevacizumab acts via VEGF inhibition, reducing angiogenesis and tumor blood supply. It is continued until progression or unacceptable toxicity, often combined with chemotherapy switches (e.g., FOLFOX → FOLFIRI + bevacizumab). **Mnemonic:** **KRAS WT + MSS → Bevacizumab** (not checkpoint inhibitors). **MSI-H/dMMR → Nivolumab** (regardless of KRAS).
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