Table 1.
The efficacy and toxicities of combinatorial therapeutic strategies of RAF inhibitors in BRAFm CRC patients
| Strategies | Drugs | N | BRAF-V600E (%) | Efficacy
|
Toxicities (%)
|
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ORR (%) | mPFS (months) (95% CI) | mOS (months) (95% CI) | Fatigue | Diarrhea | Vomiting/nausea | Rash | Lipase increase | Dry skin | Dermatitis acneiform | Abdominal pain | Arthralgia | ||||
| Doublet | |||||||||||||||
| BRAF + EGFR | Cetuximab + vemurafenib53 | 27 | 89 | 4 | 3.7 (1.8–5.1) | 7.1 (4.4–NR) | 52 | 44 | 26 | 74 | 22 | – | – | – | 44 |
| Vemurafenib + panitumumab15 | 15 | 100 | 13 | 3.2 (1.6–5.3) | 7.6 (2.1–NR) | 34 | 7 | 14 | 53 | – | 27 | – | 7 | 26 | |
| Dabrafenib + panitumumab76 | 20 | 100 | 10 | 3.5 (NA) | 13.2 (NA) | 50 | 45 | 50 | 60 | – | 40 | 60 | – | – | |
| Encorafenib + cetuximab (Phase I)56 | 26 | 96 | 19 | 3.7 (2.8–12) | NA | 50 | 19 | 46 | 19 | – | 19 | 11 | 31 | 4 | |
| Encorafenib + cetuximab (Phase II)75 | 50 | NA | 22 | 4.2 (3.4–5.4) | NR | 50 | 21 | 46 | 17 | 18 | 12 | – | 42 | – | |
| BRAF + MEK | Dabrafenib + trametinib54 | 43 | 100 | 12 | 3.5 (3.4–4) | NA | 53 | 35 | 63 | – | – | – | – | – | – |
| Triplet | |||||||||||||||
| BRAF + MEK + EGFR | Dabrafenib + trametinib + panitumumab76 | 91 | 100 | 21 | 4.2 (4.1–5.6) | 9.1 (7.6–20) | 49 | 65 | 56 | 36 | – | 54 | 59 | – | – |
| BRAF + MEK + PI3K | Encorafenib + cetuximab + alpelisib (Phase I)56 | 28 | 96 | 18 | 4.2 (4.1–5.4) | NA | 43 | 54 | 50 | 36 | – | 32 | 29 | 25 | – |
| Encorafenib + cetuximab + alpelisib (Phase II)75 | 52 | NA | 27 | 5.4 (4.1–7.2) | 15.2 (NA) | 46 | 54 | 56 | 27 | 8 | 20 | – | 40 | – | |
| BRAF + EGFR + irinotecan | Vemurafenib + cetuximab + irinotecan (Phase I)80 | 19 | 100 | 35 | 7.7 (3.1–NR) | NA | 89 | 84 | 79 | 74 | – | – | – | – | 42 |
| Vemurafenib + cetuximab + irinotecan (Phase II)81 | 54 | 100 | 16 | 4.4 (3.6–5.7) | NA | 15a | 22a | – | – | – | – | – | – | – | |
Note:
a
Grade 3/4 adverse events.
Abbreviations: BRAFm, BRAF mutation; CI, confidence interval; CRC, colorectal cancer; mPFS, median progression-free survival; mOS, median overall survival; NA, not available; NR, not reached; ORR, objective response rate.