Tom 8, Nr 3 (2022)
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Opublikowany online: 2022-03-02
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Eksport do Mediów Społecznościowych

Eksport do Mediów Społecznościowych

Leczenie ukierunkowane molekularnie chorych na zaawansowanego czerniaka skóry

Alice Indini1, Fausto Roila2, Rossana Gueli1, Francesco Grossi13, Mario Mandalà2
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.

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