Open-label, multicentre safety study of vemurafenib in 3219 patients with BRAF mutation-positive metastatic melanoma: 2-year follow-up data and long-term responders' analysis.

BACKGROUND

The orally available BRAF kinase inhibitor vemurafenib is an effective and tolerable treatment option for patients with metastatic melanoma harbouring BRAF mutations. We assessed the safety of vemurafenib in a large population of patients with few alternative treatment options; we report updated 2-year safety.

METHODS

This was an open-label, multicentre study of vemurafenib (960 mg bid) in patients with previously treated or untreated BRAF mutation-positive metastatic melanoma (cobas 4800 BRAF V600 Mutation Test). The primary end-point was safety; efficacy end-points were secondary. An exploratory analysis was performed to assess safety outcomes in patients with long duration of response (DOR) (≥12 or ≥24 months).

RESULTS

After a median follow-up of 32.2 months (95% CI, 31.1-33.2 months), 3079/3219 patients (96%) had discontinued treatment. Adverse events (AEs) were largely consistent with previous reports; the most common all-grade treatment-related AEs were arthralgia (37%), alopecia (25%) and hyperkeratosis (23%); the most common grade 3/4 treatment-related AEs were squamous cell carcinoma of the skin (8%) and keratoacanthoma (8%). In the exploratory analysis, patients with DOR ≥12 months (n = 287) or ≥24 months (n = 133) were more likely to experience grade 3/4 AEs than the overall population. No new specific safety signals were observed with longer vemurafenib exposure.

CONCLUSIONS

After 2 years' follow-up, safety was maintained in this large group of patients with BRAF mutation-positive metastatic melanoma who are more representative of routine clinical practice than typical clinical trial populations. These data suggest that long-term vemurafenib treatment is effective and tolerable without the development of new safety signals.