Targeted Therapy Drugs: Vemurafenib

Targeted Therapy Drugs: Vemurafenib-Introduction

Vemurafenib, developed by Hoffmann-La Roche Inc., a B-Raf enzyme inhibitor. It is approved for the treatment of patients with unresectable or metastatic melanoma with the BRAF V600E mutation as detected by an FDA-approved test.

Targeted Therapy Drugs: Vemurafenib-Target

The target of this drug is BRAF. BRAF belongs to a family of serine-threonine protein kinases that includes ARAF, BRAF, and CRAF (RAF1). RAF kinases are central mediators in the MAP kinase signaling cascade and exert their effect predominantly through phosphorylation and activation of MEK. This occurs following the dimerization (hetero- or homo-) of the RAF molecules. As part of the MAP kinase pathway, RAF is involved in many cellular processes, including cell proliferation, differentiation, and transcriptional regulation.

Targeted Therapy Drugs: Vemurafenib-Efficacy

The approval was based primarily on an international, randomized, open-label trial in patients with previously untreated metastatic or unresectable melanoma with the BRAFV600E mutation. The trial enrolled 675 patients; 337 patients were assigned to vemurafenib, 960 mg orally twice daily, and 338 were assigned to dacarbazine, 1000 mg/m2 intravenously, every three weeks. Treatment continued until disease progression, unacceptable toxicity, and/or consent withdrawal. The median follow-up at the time of the overall survival analysis was 6.2 and 4.5 months for the vemurafenib and dacarbazine arms, respectively. Overall survival was significantly improved in patients receiving vemurafenib compared to those receiving dacarbazine (HR=0.44; 95% CI: 0.33, 0.59; p< 0.0001, log-rank test). The median survival of patients receiving vemurafenib had not been reached (95% CI: 9.6 months, not reached) and was 7.9 months (95% CI: 7.3, 9.6) for those receiving dacarbazine. Progression-free survival (PFS) was also significantly improved in patients receiving vemurafenib (HR=0.26; 95% CI: 0.20, 0.33; p<0.0001, log-rank test). The median PFS was 5.3 (95% CI: 4.9, 6.6) and 1.6 months (95% CI: 1.6, 1.7) in the vemurafenib and dacarbazine arms, respectively. Overall response rate (complete plus partial response rates) was 48.4% (95% CI: 41.6%, 55.2%) and 5.5% (95% CI: 2.8%, 9.3%) in the vemurafenib and dacarbazine arms, respectively.

Targeted Therapy Drugs: Vemurafenib-Side Effect

The most common adverse reactions (≥30%) in patients treated with vemurafenib were arthralgia, rash, alopecia, fatigue, photosensitivity reaction, and nausea. Cutaneous squamous cell carcinomas (cuSCC), including squamous cell carcinomas of the skin and keratoacanthomas, were detected in approximately 24% of patients treated with vemurafenib. CuSCCs were managed with excision in clinical trials, and patients were able to continue treatment without dose adjustment. Other adverse reactions, sometimes severe, reported in vemurafenib-treated patients included hypersensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis, uveitis, QT prolongation, and liver enzyme laboratory abnormalities.

Targeted Therapy
What is Targeted Therapy
Targeted Therapy: Targets
Targeted Therapy for Cancer
EGFR Targeted Therapy
HER2 Targeted Therapy
VEGF Targeted Therapy
BRAF Targeted Therapy
ALK Targeted Therapy
Immune Checkpoint Targeted Therapy
Targeted Therapy Drugs
Targeted Therapy Drugs: Elotuzumab
Targeted Therapy Drugs: Necitumumab
Targeted Therapy Drugs: Daratumumab
Targeted Therapy Drugs: Ramucirumab
Targeted Therapy Drugs: Trastuzumab
Targeted Therapy Drugs: Vemurafenib
Targeted Therapy Drugs: Crizotinib
The Differences between Chemotherapy and Targeted Therapy
Side Effects of Targeted Therapy
Oral Targeted Therapy
Targeted Therapy Resistance
How does Targeted Therapy Work