Search

Introduction. Melanoma is a heterogeneous group of tumours with poor prognosis if the disease is metastatic. More than half of patients with melanoma of the skin have detectable mutations in the BRAF gene. Vemurafenib is the BRAF kinase inhibitor used in the treatment of patients with advanced melanoma with the BRAF mutation. This improves time to progression-free survival and overall survival in patients with this diagnosis. The aim of the study was to analyse the results of treatment and safety of vemurafenib in patients treated during the Polish drug programme. Materials and methods .Between October 2013 and April 2015 a total of 189 patients were treated, 90 women and 99 men, who had previously been diagnosed with unresectable/metastatic melanoma with BRAF V600 mutation. Patients received vemurafenib in 960 mg dose twice per day. The estimated progression-free survival, overall survival and adverse events were assessed. For the survival analysis the Kaplan-Meier method and log-rank test (log-rank) for multi-factor analysis were used. Results. In the first evaluation of the effectiveness of treatment, 8 patients (4.3%) had a complete response, 75 patients (39.7%) partial response, 62 patients (32.8%) had stable disease, and 44 patients (23.2%) had progression of the disease. The disease was controlled in 76.7% of patients. After progression during the therapy with vemurafenib 27% of the patients received subsequent lines of systemic therapy. Twenty-eight patients received chemotherapy and 22 patients immunotherapy with ipilimumab. During the last analysis dated 5 September 2015, the median observation time for still living patients was 8 months (range 3–26). Median progression-free survival was 6.7 months. The median overall survival was 12 months. 146 patients (77%) had adverse events, mostly in the form of dermal toxicity of Grades 1 and 2. Thirty-two patients (17%) presented with side effects of the 3rd and 4th grades of toxicity. Two patients had to stop the treatment due to the toxicity. There were no deaths reported due to the toxicity of treatment. Conclusions. The multicentre analysis confirmed the efficacy and safety of vemurafenib in routine clinical practice in a heterogeneous group of advanced melanomas with BRAF mutation. We confirmed the importance of the known prognostic factors for overall survival in this group of patients, such as lactate dehydogenaze activity (LDH) and ECOG performance status. The current survival of patients with the metastatic melanomas with BRAF mutations are longer than those observed in historical groups.

Podstawą klinicznej diagnostyki roznicowej czerniakow skory i kwalifikacji do biopsji wycinającej jest obecnie dermoskopia. Dla ustalenia rozpoznania i określenia najwazniejszych czynnikow rokowniczych podstawowe znaczenie ma biopsja wycinająca podejrzanych w kierunku wczesnego czerniaka zmian barwnikowych skory (wyciecie calej grubości skory i powierzchownej warstwy tkanki tluszczowej). Wczesne rozpoznanie i chirurgiczne usuniecie czerniaka nie tylko poprawia rokowanie, ale daje szanse wyleczenia okolo 90% chorych. Kolejne etapy postepowania terapeutycznego obejmują kwalifikacje chorych do radykalnego wyciecia blizny po biopsji wycinającej z wlaściwymi marginesami oraz wykonania biopsji wezla wartowniczego. W przypadku przerzutow do regionalnych wezlow chlonnych postepowaniem z wyboru jest wykonanie radykalnej limfadenektomii. Zaleca sie wlączanie chorych na czerniaki skory o wysokim ryzyku nawrotu (przerzuty do wezlow chlonnych i/lub owrzodzenie pierwotnej zmiany) do prospektywnych badan klinicznych nad leczeniem uzupelniającym. Obecnośc przerzutow odleglych wiąze sie ze zlym rokowaniem. W sytuacji uogolnienia nowotworu konieczne jest wykonanie badania w kierunku mutacji genu BRAF . Dlugoletnie przezycia dotyczą glownie chorych poddanych resekcji pojedynczych ognisk przerzutowych. W systemowym leczeniu — przede wszystkim pierwszej linii — u chorych z obecnością mutacji BRAF V600 znajduje zastosowanie inhibitor BRAF — wemurafenib lub dabrafenib (preferencyjnie w skojarzeniu z inhibitorem MEK) oraz — niezaleznie od statusu mutacji BRAF — immunoterapia przeciwcialami anty-PD-1 (niwolumab lub pembrolizumab), ewentualnie ipilimumab (przeciwcialo anty-CTLA4).

The incidence of cutaneous melanoma is constantly increasing. The primary treatment in early stage of disease re­mains surgery. New therapeutic strategies such as immunotherapy or selective BRAF inhibitors — vemurafenib and dabrafenib, have improved outcomes of treatment in the group of patients with stage IV melanoma. In Poland still only vemurafenib is available in routine clinical practice. In this article we present clinical experiences in treating of BRAF-positive metastatic melanoma patients with use of vemurafenib.