Tom 8, Nr 3 (2022)
Artykuł przeglądowy
Opublikowany online: 2022-03-02
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Leczenie ukierunkowane molekularnie chorych na zaawansowanego czerniaka skóry
Onkol Prakt Klin Edu 2022;8(3):214-226.
Streszczenie
Leki ukierunkowane na szlak kinazy białkowej aktywowanej mitogenami (MAPK), inhibitory BRAF i MEK, istotnie poprawiły przeżywalność pacjentów z czerniakiem z mutacją BRAF V600. Dotychczas zarejestrowano trzy skojarzone terapie celowane na podstawie wyników czterech badań klinicznych III fazy z randomizacją (COMBI-D, COMBI-V, CoBRIM i COLUMBUS). W badaniach tych leczenie skojarzone inhibitorami BRAF i MEK wykazało przewagę nad monoterapią inhibitorem BRAF, z dość podobnymi wynikami we wszystkich badaniach w zakresie odsetka odpowiedzi (63–70%), OS (mediana > 24 miesięcy) i PFS (wartości mediany 11–14 mies.). W związku z tym decyzje dotyczące zastosowania określonej terapii skojarzonej podejmowane w praktyce klinicznej opierają się głównie o różnice w zakresie profili toksyczności. Pomimo skuteczność tych leków, problemem jest oporność na leczenie, która rozwija się zarówno w trakcie immunoterapii jak i terapii ukierunkowanej molekularnie. W związku z tym dotychczas nie uzgodniono najlepszej sekwencji terapii u pacjentów z czerniakiem z mutacją BRAF umożliwiającej uzyskanie optymalnych wyników dotyczących przeżycia. Podjęto badania nad kilkoma strategiami dalszej poprawy wyników leczenia ukierunkowanego molekularnie poprzez skojarzenie i/lub sekwencyjne stosowanie różnych terapii. W niniejszym przeglądzie przedstawiono charakterystykę molekularną czerniaka skóry, zwłaszcza mutacji BRAF oraz dowody uzasadniające zastosowanie terapii ukierunkowanych molekularnie, ich skuteczność i toksyczność oraz perspektywy leczenia pacjentów z tym nowotworem w przyszłości.
Słowa kluczowe: BRAFMAPKczerniakchoroba przerzutowaterapie ukierunkowane molekularnie
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