| Drug | Brand Name | BRAF Target | Approved Indications (General) | Key Toxicities | Clinical Pearls |
|---|---|---|---|---|---|
| Vemurafenib | Zelboraf | BRAF V600E | – Unresectable/metastatic melanoma (BRAF V600E) – Erdheim-Chester disease (BRAF V600E) |
Photosensitivity, rash, QT prolongation, arthralgia, cuSCC/keratoacanthoma | First approved BRAF inhibitor (2011). Often combined with cobimetinib. |
| Dabrafenib | Tafinlar | BRAF V600E/K | – Melanoma (unresectable/metastatic, adjuvant, BRAF V600E/K) – NSCLC (BRAF V600E, with trametinib) – Anaplastic thyroid cancer (BRAF V600E, with trametinib) |
Pyrexia, hyperglycemia, cardiomyopathy, uveitis, cuSCC | Preferred over vemurafenib due to tolerability. Standard combo: dabrafenib + trametinib. |
| Encorafenib | Braftovi | BRAF V600E/K | – Melanoma (BRAF V600E/K, with binimetinib) – Metastatic colorectal cancer (BRAF V600E, with cetuximab ± binimetinib) |
Arthralgia, fatigue, elevated LFTs, nausea, QT prolongation, lower incidence of cuSCC vs others | Longer half-life → lower resistance risk. Combo: encorafenib + binimetinib. |
| Sorafenib (multikinase inhibitor, also hits BRAF) | Nexavar | BRAF (non-selective), VEGFR, KIT, FLT3 | – Hepatocellular carcinoma (HCC) – Renal cell carcinoma (RCC) – Differentiated thyroid carcinoma |
Hand-foot syndrome, diarrhea, hypertension, rash | Broader kinase inhibitor, not selective for BRAF. |
| Others under study / niche use | – | – | – Pediatric low-grade gliomas (dabrafenib + trametinib) – Rare histiocytic disorders (LCH, Erdheim-Chester) |
– | Expanding use in targeted pediatric oncology. |
Class-Wide Points
- Mechanism: Inhibit mutated BRAF kinase → block MAPK/ERK signaling, reducing tumor cell proliferation.
- Most active against: BRAF V600E mutation; some cover V600K (dabrafenib, encorafenib).
- Combination with MEK inhibitors is standard: reduces resistance, improves survival, lowers cutaneous malignancies.
- Beyond melanoma:
- NSCLC (dabrafenib + trametinib, FDA-approved)
- Colorectal cancer (encorafenib + cetuximab, FDA-approved)
- Thyroid cancer (dabrafenib + trametinib, FDA-approved)
- Histiocytic neoplasms (vemurafenib for Erdheim-Chester disease, off-label in LCH).
- Toxicities:
- Dermatologic: rash, SCC, keratoacanthoma
- Cardiovascular: QT prolongation, cardiomyopathy
- Ocular: uveitis, retinal detachment
- Pyrexia (dabrafenib especially)
- Photosensitivity (vemurafenib)
Key Takeaway for Oncology Pharmacist:
BRAF inhibitors are cornerstone therapy not only in melanoma but also in NSCLC, colorectal, thyroid cancer, and histiocytic disorders — always in BRAF V600E/K mutation-positive tumors. Combination with MEK inhibitors is the modern standard to improve outcomes and reduce resistance.
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