Drug updated on 4/10/2024
| Dosage Form | Tablet (oral; 240 mg) |
| Drug Class | Kinase inhibitors |
| Ongoing and Completed Studies | ClinicalTrials.gov |
Indication
- For the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test.
- For the treatment of patients with Erdheim Chester Disease with BRAF V600 mutation.
Summary
- Vemurafenib (Zelboraf) is used in the treatment of metastatic melanoma with BRAF V600 mutations and Erdheim-Chester Disease with BRAF V600 mutation, showing prominent efficacy when compared to other treatments.
- Fifteen studies on vemurafenib's safety and effectiveness were reviewed.
- PD-(L)1/BRAF/MEK inhibitor triplets, which include vemurafenib combinations, were found superior to dual checkpoint inhibitor combinations such as ipilimumab/nivolumab in terms of progression-free survival (PFS) and overall response rate (ORR), but these combinations are associated with higher toxicity rates.
- Treatments pairing BRAF inhibitors like vemurafenib with MEK inhibitors demonstrated notable efficacy for advanced melanoma; however, encorafenib + binimetinib might be superior in efficacy and have a more favorable safety profile relative to vemurafenib combinations.
- Dermatological adverse events including cutaneous squamous cell carcinoma, rash, photosensitivity, among others, are common among patients treated with Zelboraf; cardiovascular adverse events also warrant close monitoring, especially when combination therapy involving both BRAF & MEK inhibitors is administered.
- For Erdheim-Chester Disease patients carrying the BRAF V600 mutation, Zelboraf has shown significant strides, although its tolerance level varies from patient to patient, requiring careful management due to side effects.
- Adjuvant therapy using targeted treatments like Zelboraf shows significant recurrence-free survival benefits across various patient subgroups, such as those based on age or specific genetic markers, e.g., presence of a particular type of BRAF mutation seems particularly beneficial for outcomes under combination therapies involving BRAF/MEK inhibition.
- Zelboraf remains an important option given its marked influence over progression-free and overall survival rates in patients with melanoma or Erdheim-Chester Disease; however, its use is challenged by higher toxicity profiles compared to some alternative regimens.
Product Monograph / Prescribing Information
| Document Title | Year | Source |
|---|---|---|
| Zelboraf (vemurafenib) Prescribing Information. | 2020 | Genentech USA, Inc., South San Francisco, CA |
Systematic Reviews / Meta-Analyses
Clinical Practice Guidelines
| Document Title | Year | Source |
|---|---|---|
| Systemic Therapy for Melanoma: ASCO Guideline Update. | 2023 | Journal of Clinical Oncology |
| Melanoma—the therapeutic considerations in the clinical practice. | 2023 | Palliative Medicine and Palliative Care for Incurable Cancer |
| Erdheim-Chester Disease. | 2022 | Leukemia and Lymphoma Society |
| Clinical Practice Guideline on Melanoma From the Spanish Academy of Dermatology and Venereology (AEDV). | 2021 | Actas Dermo-Sifiliográficas |
| Systemic therapy for melanoma: ASCO guideline. | 2020 | Journal of Clinical Oncology |
| Erdheim-Chester disease: consensus recommendations for evaluation, diagnosis, and treatment in the molecular era. | 2020 | Blood |
| Cutaneous melanoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. | 2019 | Annals of Oncology |
| Cutaneous melanoma, version 2.2019. | 2019 | Journal of the National Comprehensive Cancer Network |