Vemurafenib
- OralVemurafenibZelborafGiven as monotherapy or in combination with cobimetinib (MEK inhibitor)
- Mechanism of Action
- Normally, activation of RAS pathway via receptor tyrosine kinases (RTKs) results in activation of BRAF which then activates MEK, and in turn, ERK.
- The RAS / RAF / MEK / ERK pathway stimulates cell proliferation and survival.
- In melanoma with BRAF mutations, the mutant BRAF (most commonly V600E) is constitutionally active.
- BRAF inhibitors bind to mutant BRAF V600 and, in turn, inhibit cellular proliferation in cells with BRAF mutations.
Clinical Use
- Indications
- Unresectable stage III or metastatic (stage IV) melanoma with BRAF (V600) mutation
- Adverse Effects
- Rash
- Alopecia
- Hyperkeratosis
- Papillomas / squamous cell carcinomas
- Nausea / vomiting / diarrhoea
- Arthralgia / myalgia
- Headache