Safety of vemurafenib in patients with BRAF V600 mutated metastatic melanoma: the Spanish experience.

Abstract

Vemurafenib tolerability was assessed in a large, open-label, multicentre study in patients with BRAF V600 mutated advanced melanoma. We investigated safety, tolerability and efficacy of vemurafenib in Spanish patients participating in that study. Patients with previously treated or treatment-naive, unresectable stage IIIC or stage IV, BRAF V600 mutation-positive melanoma received vemurafenib 960mg twice daily until disease progression, unacceptable toxicity, withdrawal of consent or death. The primary endpoint was safety; secondary endpoints included overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). 301 Spanish patients were included, 70% with M1c disease, 22% with brain metastases and 51% with prior systemic therapy for metastatic disease. Most frequent adverse events included fatigue (48%), arthralgia (45%), rash (41%), photosensitivity (34%) and skin neoplasms (21%). Grade 3/4 adverse events occurred in 156 patients (52%), including cutaneous squamous cell carcinoma (including keratoacanthoma; 16%), fatigue (6%) and arthralgia (5%). The ORR was 28% (95% CI 23-34%). Responses occurred in patients with brain metastases (18%), elevated baseline lactate dehydrogenase (19%) and poor performance status (15%), and elderly patients (22%). Median PFS was 5.8 (95% CI 5.0-6.4) months; median OS was 10.5 (95% CI 9.5-13.5) months. Our results for Spanish patients in the vemurafenib safety study indicate similar efficacy and a comparable safety profile in Spanish patients with no new safety signals compared with the overall population. Clinical benefit was demonstrated in poor-prognosis patients and in those with favourable baseline characteristics, suggesting that poor-prognosis patients may also benefit from vemurafenib treatment.