Adjuvant treatment of melanoma

Incidencija melanoma povećava se brže od bilo koje druge maligne bolesti i predstavlja važan javnozdravstveni problem. Potpuno kirurško odstranjenje primarna je metoda liječenja melanoma u ranim stadijima bolesti. Nakon kompletnog kirurškog odstranjenja, rizik povrata bolesti ovisi o stadiju bolesti. Desetogodišnje preživljenje se kreće od 98% za stadij IA do 24% za stadij IIID. Cilj adjuvantne terapije je uništiti mikrometastaze i smanjiti stopu povrata bolesti. Interferon α-2b je dvadeset godina bio jedina odobrena terapija za adjuvantno liječenje melanoma, usprkos upitnoj učinkovitosti i čestim nuspojavama. Uspjeh inhibitora imunoloških kontrolnih točaka i ciljane terapije u liječenju uznapredovalog melanoma otvorio je put kliničkim ispitivanjima u adjuvantnom liječenju melanoma. Rezultati provedenih kliničkih ispitivanja doveli su do odobrenja PD-1 inhibitora i BRAF/MEK inhibitora za adjuvantno liječenje visokorizičnog melanoma. Rezultati ispitivanja pokazali su učinak na produljenje preživljenja bez recidiva, no učinak na ukupno preživljenje do sada nije dosegnut. Zbog nepostojanja pouzdanih prediktivnih biomarkera poseban problem predstavljaju pitanja koga sve liječiti adjuvantnom terapijom i koju terapiju odabrati. PD-1 inhibitori i BRAF/MEK inhibitori razlikuju se u načinu primjene i profilu nuspojava. Trenutno je adjuvantno liječenje odobreno za stadije IIB, IIC, III i operirane stadije IV. Ovaj rad prezentira dosadašnje dosege u adjuvantnom liječenju melanoma, izdvajajući najznačajnija klinička ispitivanja.The incidence of melanoma is increasing faster than of any other malignant disease and represents an important public health problem. Complete surgical removal is the primary method of treating melanoma in the early stages of the disease. After complete surgical removal, the risk of disease recurrence depends on the stage of the disease. Ten-year survival ranges from 98% for stage IA to 24% for stage IIID. The goal of adjuvant therapy is to destroy micrometastases and reduce the rate of disease recurrence. Interferon α-2b had been the only approved therapy for the adjuvant treatment of melanoma for twenty years, despite its questionable efficacy and frequent side effects. The success of immune checkpoint inhibitors and targeted therapies in the treatment of advanced melanoma has paved the way for clinical trials in the adjuvant treatment of melanoma. The results of the conducted clinical trials led to the approval of PD-1 inhibitors and BRAF/MEK inhibitors for the adjuvant treatment of highrisk melanoma. The results of the trial showed an effect on prolonging survival without recurrence, but the effect on overall survival has not been reached so far. Due to the lack of reliable predictive biomarkers, the questions of whom to treat with adjuvant therapy and which therapy to choose, pose a particular problem. PD-1 inhibitors and BRAF/MEK inhibitors differ in their mode of administration and side effect profile. Currently, adjuvant treatment is approved for stages IIB, IIC, III, and operated stage IV. This paper presents the achievements so far in the adjuvant treatment of melanoma, highlighting the most important clinical trials