Table 3.
BRAF and KRAS mutations as prognostic factors in clinical studies of first-line treatment for mCRC
| Name of study | Phase of clinical trial | Therapeutic strategy | Key outcomes in patients | Prognostic finding |
|---|---|---|---|---|
| MRC COIN | III | OFC | Median OS, 8.8 vs 20.1 months for patients with wild-type BRAF (P < 0.001); median OS, 14 vs 20.1 months for patients with wild-type KRAS (P < 0.001) | KRAS and BRAF mutations have a strong prognostic effect |
| CRYSTAL | III | FOLFIRI, cetuximab | Median OS, 8.8 vs 20.1 months for patients with wild-type BRAF (P < 0.001); median OS, 14 vs 20.1 months for patients with wild-type KRAS (P < 0.001) | KRAS and BRAF mutations are important indicators of poor prognosis |
| PRIME | III | FOLFOX4, panitumumab | In the mutant KRAS stratum, PFS was significantly reduced in the panitumumab–FOLFOX4 arm vs the FOLFOX4 arm; median OS, 15.5 vs 19.3 months, respectively (P = 0.068) | KRAS testing is important for patients with mCRC |
| CAIRO2 | III | CBC | Median PFS, 8.1 and 12.5 months in patients with KRAS-mutant vs 10.5 and 10.6 months in patients with KRAS wild-type tumors in two arms | Mutation status of the KRAS gene was a predictor of outcome in the cetuximab group |
| Median OS, 17.2 and 24.9 months in patients with KRAS-mutant tumors vs 21.8 and 22.4 months in patients with KRAS wild-type tumors with CB and CBC, respectively | ||||
| CAIRO2 | III | CBC | Median PFS, 5.9 and 6.6 months in patients with BRAF-mutant tumors vs 12.2 and 10.4 months in patients with BRAF wild-type tumors in two arms | BRAF mutation was a negative prognostic marker in patients with mCRC |
| Median OS, 15.0 and 15.2 months in BRAF-mutant vs 24.6 and 21.5 months in BRAF wild-type tumors in two arms | ||||
| NORDIC-VII | III | Nordic FLOX, cetuximab | ORRs, 20% in patients with BRAF-mutant tumors vs 50% in those with BRAF wild-type tumors (P < 0.01) | Presence of BRAF mutations was a strong negative prognostic factor |
| TAILOR | III | FOLFOX-4, cetuximab | Median PFS, 2.0 in patients with BRAF-mutant tumors vs 9.3 months in patients with BRAF wild-type tumors | Mutation status of the BRAF gene was a predictor of outcome in the cetuximab group |
| Pooled analysis of CAIRO, CAIRO2, COIN, and FOCUS phase 3 studies | III | CBC | Median PFS, 6.2 in BRAF-mutant vs 7.7 months in BRAF wild-type tumors | BRAF-mutant status was a biomarker conferring poor prognosis in mCRC |
| Median OS, 11.4 in BRAF-mutant vs 17.2 months in BRAF wild-type tumors |
BRAF, V-raf murine sarcoma viral oncogene homolog B1; KRAS, V-Ki-ras2 Kirsten ratsarcoma viral oncogene homolog; OFC, oxaliplatin, fluoropyrimidine, cetuximab; FOLFIRI, irinotecan, infusional fluorouracil, leucovorin; FOLFOX4, infusional fluorouracil, leucovorin, and oxaliplatin; CBC, capecitabine, oxaliplatin, bevacizumab, cetuximab.