Table 3.
Summary of primary brain tumor types and clinical data supporting RAF-targeted therapy in each tumor type.
| Inhibitor | |||||||
|---|---|---|---|---|---|---|---|
| Brain Tumor Type | Mutation | Incidence | Type I RAF | Type II RAF | RAF Dimer | MEK | RAF + MEK |
| Pilocytic astrocytoma | KIAA1549–BRAF | 60–70% [42,69] | Not active [33] | TAK-580 (NCT03429803) | Selumetinib [66] Binimetinib [67] (NCT02285439) | ||
| V600E | 10% [22,42,72] | Dabrafenib/Trametinib case series [73] | |||||
| Pediatric low-grade astrocytoma | V600E | 20–35% [72,74] | Dabrafenib [75] Vemurafenib (NCT01748149, NCT03220035) | PLX8394 (NCT02428712) | TAK-580 (NCT03429803) | Trametinib [76] (NCT02124772) | Dabrafenib/Trametinib (NCT02684058; NCT02124772) |
| KIAA1549–BRAF | Preclinical activity [33] | ||||||
| Pediatric high-grade astrocytoma | V600E | 10–20% [23,77] | Vemurafenib (NCT01748149, NCT03220035) | Dabrafenib/Trametinib (NCT02684058) | |||
| Adult low-grade astrocytoma | V600E | 5–15% [24] | [15] | Dabrafenib/Trametinib (NCT02034110) | |||
| Adult high-grade astrocytoma | V600E | 3% [22,24,78] | Vemurafenib [15] | Dabrafenib/Trametinib [79] (NCT02034110) Encorafenib/Binimetinib (NCT03973918) |
|||
| Pleomorphic xanthoastrocytoma | V600E | 70% [22] | Vemurafenib [15] | Dabrafenib/Trametinib [79] (NCT02034110) Encorafenib/Binimetinib (NCT03973918) |
|||
| Ganglioglioma | V600E | 50% [72,80] | Vemurafenib case reports [15,81,82,83,84,85,86,87] Dabrafenib case [81] |
Case reports [82,88,89,90] | |||
| Papillary craniopharyngioma | V600E | 95% [27] | Dabrafenib/Trametinib (NCT03224767) | ||||