Colorectal cancer: lines of therapy
18 standard-of-care settings across 6 lines and 8 biomarker subgroups. Rows come from the cancer page's standard of care; the grid places each on its line and subgroup.
| Line | All comers | BRAF | FRα | HER2 | KRAS G12C | MSI-H / dMMR | pMMR / MSS | RAS |
|---|---|---|---|---|---|---|---|---|
| Screening, prevention and diagnosis | 2 | · | · | · | · | · | · | · |
| Early / localised | 2 | · | · | · | · | · | · | · |
| Locally advanced | · | · | · | · | · | 2 | 2 | · |
| Advanced, first line | · | 1 | · | 1 | 1 | 2 | 1 | 2 |
| Third line and beyond | · | · | 1 | · | · | · | · | · |
| Special situations | 1 | · | · | · | · | · | · | · |
Screening, prevention and diagnosis
| Subgroup | Setting | Approach | Products and trials | Guideline | Evidence |
|---|---|---|---|---|---|
| All comers | Screening | Colonoscopy, FIT, Cologuard, Shield blood test from age 45. | NCCN Guidelines: Colon Cancer | 39 | |
| All comers | Screening (average risk, age 45-75) | Colonoscopy every 10 years, annual FIT, multitarget stool DNA every 3 years, CT colonography, or the Shield blood test every 3 years; start at 45 (USPSTF 2021). Lynch carriers: colonoscopy every 1-2 years from age 20-25. | NCCN · NCCN Colorectal Cancer Screening | 63 |
Early / localised
| Subgroup | Setting | Approach | Products and trials | Guideline | Evidence |
|---|---|---|---|---|---|
| All comers | Stage II-III | Surgery; adjuvant chemotherapy guided by risk and (in trials) ctDNA; exercise programme. | NCCN Guidelines: Colon Cancer | 68 | |
| All comers | Stage I-II colon | Surgical resection; observation for stage I and low-risk stage II. High-risk stage II (T4, obstruction, <12 nodes, LVI): consider 3-6 months fluoropyrimidine ± oxaliplatin; ctDNA-negative patients can safely omit (DYNAMIC). dMMR stage II derives no benefit from 5-FU alone. | 83 |
Locally advanced
| Subgroup | Setting | Approach | Products and trials | Guideline | Evidence |
|---|---|---|---|---|---|
| MSI-H / dMMR | Stage III colon, dMMR | Resection then FOLFOX + atezolizumab for 12 months (ATOMIC, 3-year DFS 86% vs 77%). Neoadjuvant nivolumab + ipilimumab (NICHE-2) is an alternative under evaluation. | 88 | ||
| MSI-H / dMMR | Locally advanced rectal, dMMR | Dostarlimab monotherapy for 6 months with organ preservation (MSK cohort 100% cCR; AZUR-1 registrational, PDUFA February 2027). Chemoradiation and surgery reserved for non-responders. | 82 | ||
| pMMR / MSS | Stage III colon, pMMR | Resection then adjuvant CAPOX for 3 months (T1-3 N1, low risk) or FOLFOX/CAPOX for 6 months (T4 or N2), per IDEA. | NCCN · Category 1 | 82 | |
| pMMR / MSS | Locally advanced rectal, pMMR | Total neoadjuvant therapy: short-course radiation or long-course chemoradiation plus FOLFOX/CAPOX, then TME surgery or watch-and-wait for clinical complete response (OPRA). Non-operative management for select cCR. | 91 |
Advanced, first line
| Subgroup | Setting | Approach | Products and trials | Guideline | Evidence |
|---|---|---|---|---|---|
| BRAF | Metastatic, BRAF V600E | First line: encorafenib + cetuximab + mFOLFOX6 or FOLFIRI (BREAKWATER, OS 30.3 vs 15.1 months). Later line: encorafenib + cetuximab (BEACON). | 87 | ||
| HER2 | Metastatic, HER2-amplified, RAS wild-type | Tucatinib + trastuzumab (MOUNTAINEER) or trastuzumab deruxtecan 5.4 mg/kg (DESTINY-CRC02) after chemotherapy; MOUNTAINEER-03 tests first-line use. | 97 | ||
| KRAS G12C | Metastatic, KRAS G12C | Sotorasib + panitumumab (CodeBreaK 300) or adagrasib + cetuximab after chemotherapy; first-line trials ongoing. | 90 | ||
| MSI-H / dMMR | Metastatic, dMMR | Checkpoint inhibitors; organ preservation in rectal cancer. | NCCN Guidelines: Colon Cancer | 98 | |
| MSI-H / dMMR | Metastatic, dMMR/MSI-high, first line | Pembrolizumab (KEYNOTE-177) or nivolumab + ipilimumab (CheckMate 8HW, PFS 54 months); nivolumab monotherapy alternative. Chemotherapy reserved for IO-refractory disease. | NCCN · Category 1 (pembrolizumab, nivolumab + ipil…ESMO-MCBS · 4 (pembrolizumab) | 98 | |
| pMMR / MSS | Metastatic, MSS | Doublet/triplet chemotherapy + biologic by genotype; targeted combinations for BRAF, KRAS G12C, HER2. | NCCN Guidelines: Colon Cancer | 87 | |
| RAS | Metastatic, RAS/BRAF wild-type, left-sided | FOLFOX or FOLFIRI + panitumumab or cetuximab (PARADIGM OS 37.9 months); bevacizumab if anti-EGFR contraindicated. Maintenance fluoropyrimidine ± biologic after induction. | 95 | ||
| RAS | Metastatic, RAS-mutant or right-sided (non-G12C) | FOLFOX, FOLFIRI, or FOLFOXIRI + bevacizumab; anti-EGFR contraindicated. KRAS G12D and other alleles: RAS(ON) inhibitors in trials. | 98 |
Third line and beyond
Special situations
Sequence and caution pairings
Regimens in the library
Lines and subgroups are parsed from the setting text of each standard-of-care row and can misclassify an unusual phrasing; the row’s own setting is always shown. Guideline chips reflect the NCCN category and ESMO-MCBS grade recorded on the cancer page, checked on its stated date. Not medical advice.