Drug updated on 9/5/2024
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.
Latest News
Summary
- Zelboraf (vemurafenib) is indicated for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test and for the treatment of patients with Erdheim Chester Disease with BRAF V600 mutation.
- This summary is based on the review of 14 systematic review(s)/meta-analysis(es). [1-14]
- In patients with advanced melanoma, Ipilimumab/Nivolumab and Relatlimab/Nivolumab demonstrated no significant differences in progression-free survival (PFS) and the overall response rate (ORR) (HR = 0.99, 95% CI 0.75-1.31; RR = 0.99, 95% CI 0.78-1.27).
- PD-(L)1/BRAF/MEK inhibitors (triplet combinations) showed superior PFS (HR = 0.56, 95% CI 0.37-0.84) and ORR (RR = 3.07, 95% CI 1.61-5.85) compared to Ipilimumab/Nivolumab in the treatment of advanced melanoma.
- In BRAF-V600 mutation-positive patients, Dabrafenib + Trametinib demonstrated favorable PFS and OS compared to monotherapies (Dabrafenib, Vemurafenib) and was comparable to other combination therapies (Encorafenib + Binimetinib and Cobimetinib + Vemurafenib).
- For adjuvant therapy in Stage III BRAF-mutant melanoma, Dabrafenib + Trametinib provided a significant recurrence-free survival (RFS) benefit (HR = 0.49, 95% CI 0.40-0.59), while Nivolumab/Ipilimumab offered the highest RFS benefit in Stage IV melanoma (HR = 0.23, 97.5% CI 0.12-0.45).
- Grade ≥3 Treatment-Related Adverse Events (TRAEs): Ipilimumab/Nivolumab has the highest risk of ≥G3 TRAEs, while Relatlimab/Nivolumab shows a trend towards a lower risk (RR = 0.71, 95% CI 0.30-1.67).
- Serious Adverse Events (SAEs): Encorafenib + Binimetinib has fewer SAEs compared to Vemurafenib + Cobimetinib (OR = 0.51, 95% CrI 0.29-0.91) and Atezolizumab + Vemurafenib + Cobimetinib (OR = 0.41, 95% CrI 0.21-0.82).
- Specific Adverse Events: Vemurafenib is associated with the highest incidence of cutaneous SCC, rash, photosensitivity, and KA; combined BRAF and MEK inhibitors increase the risk of pulmonary embolism, decreased LVEF, and arterial hypertension compared to BRAF inhibitor monotherapy (RR: 4.36, 3.72, 1.49 respectively).
- Population Types and Subgroup Considerations: Nivolumab/Ipilimumab shows the highest RFS benefit in Stage IV Malignant Melanoma, Dabrafenib/Trametinib shows significant RFS benefit in Stage III BRAF-Mutant Melanoma, BRAF mutation presence is associated with higher RFS rates, adjuvant therapy effectiveness is not influenced by patient age, and non-ulcerated melanoma cases have lower RFS with immune checkpoint inhibitor monotherapy. Additionally, in terms of safety, patients under 55 years of age have a higher risk of decreased LVEF with combined BRAF and MEK inhibitors, and those with follow-up time over 15 months have a higher risk of pulmonary embolism with the same combination.
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 |