Vemurafenib in patients with BRAF(V600) mutation-positive melanoma with symptomatic brain metastases: Final results of an open-label pilot study

BACKGROUND & AIM: Brain metastases are frequent in patients with metastatic melanoma, indicating poor prognosis. We investigated the BRAF kinase inhibitor vemurafenib in patients with advanced melanoma with symptomatic brain metastases. METHODS: This open-label trial assessed vemurafenib (960mg twice a day) in patients with BRAF(V600) mutation-positive metastatic melanoma with non-resectable, previously treated brain metastases. The primary end-point was safety. Secondary end-points included best overall response rate, and progression-free and overall survival. RESULTS: Twenty-four patients received vemurafenib for a median treatment duration of 3.8 (0.1-11.3) months. The majority of discontinuations were due to disease progression (n=22). Twenty-three of 24 patients reported at least one adverse event (AE). Grade 3 AEs were reported in four (17%; 95% confidence interval [CI], 4.7-37.4%) patients and included cutaneous squamous cell carcinoma in four patients. Median progression-free survival was 3.9 (95% CI, 3.0-5.5) months, and median survival was 5.3 (95% CI, 3.9-6.6) months. An overall partial response (PR) at both intracranial and extracranial sites was achieved in 10 of 24 (42%; 95% CI, 22.1-63.4) evaluable patients, with stable disease in nine (38%; 95% CI, 18.8-59.4) patients. Of 19 patients with measurable intracranial disease, seven (37%) achieved >30% intracranial tumour regression, and three (16%; 95% CI, 3.4-39.6%) achieved a confirmed PR. Other signs of improvement included reduced need for corticosteroids and enhanced performance status. CONCLUSIONS: Vemurafenib can be safely used in patients with advanced symptomatic melanoma that has metastasised to the brain and can result in meaningful tumour regression

Long-term recurrence rate of large and difficult to treat cutaneous squamous cell carcinomas after superficial radiotherapy

Background: Surgical excision is the gold standard for cutaneous squamous cell carcinoma (cSCC), however its application is limited in specific cases. Superficial radiotherapy (RTx)is an alternative treatment option, but long-term follow-up data are limited. Objective: To determine the outcome of superficial RTx of cSCC in correlation to histological differentiation grade and tumor localization. Methods: The outcome of 180 large cSCCs after superficial RTx between 1960 and 2004 was retrospectively reviewed. Results: Mean tumor size was 3.5 cm 2 (SD 7.5) and mean follow-up period was 4.9 years (SD 4.7). Relapse-free survival was 95.8 and 80.4% after 1 and 10 years. Two-year relapse-free survival was 94.8% for good, 88.9% for moderate and 85.7% for poor differentiated tumors. Five-year relapse-free survival was highest in cSCCs located around the eyes (100%) and cheeks (90.9%). Conclusion: Superficial RTx is an effective alternative for cSCC if surgery is difficult due to localization or concomitant disease