Za bolnike z neoperabilnimi hepatocelularni karcinom (HCC), so možnosti zdravljenja prve izbire omejene, vključno z lokalno ablacijo, arterijsko usmerjeno terapijo ali zunanjo radioterapijo ali kemoterapijo. Sorafenib (Dogime) je trenutno edini odobren sistem za bolnike z neoperabilnim HCC. Načrt spolnega zdravljenja. Leta 2017 je FDA odobrila regorafenib (Stivarga) in nivolumab (Opdivo) kot drugi možnosti zdravljenja za bolnike, ki so predhodno prejemali sorafenib. Raziskovalci verjamejo, da kombinacija zaviralec PD-L1 durvalumab (Imfinzi) in zaviralec CTLA-4 tremelimumab sta lahko najprimernejša kombinacija kliničnega zdravljenja.
Randomizirano, multicentrično preskušanje faze III HIMALAYA (NCT03298451) je razdelilo predhodno nezdravljene, neoperabilne bolnike s HCC v štiri skupine: 2 različni režimi zdravljenja s kombiniranim zdravljenjem z durvalumabom in tremelimumabom, monoterapija z durvalumabom in sorafenib Monoterapija (slika). Raziskovalci so uporabili skupno preživetje (OS) kot primarno končno točko in čas do napredovanja, preživetje brez napredovanja bolezni (PFS) in stopnjo objektivnega odziva (ORR) kot sekundarne končne točke.
Durvalumab is a human IgG monoclonal antibody, a PD-L1 inhibitor that binds to PD-1 and CD80, allowing T cells to recognize and kill tumor cells without the need for antibody-dependent and cell-mediated cytotoxic activity. Tremelimumab has a similar mechanism, inhibiting CTLA-4, a cell surface receptor mainly expressed in activated T cells. The hypothesis is that inhibition of CTLA-4 will increase the activity of PD-L1 inhibitors.
In the previous phase I / II study, 40 patients with HCC evaluated the safety and tolerability of the combination. The confirmed ORR was 17.5%, of which 7 patients had partial responses (7/40 patients), and the median response time was 8 weeks. The combination is well tolerated and there is no danger signal in patients with unrespectable HCC. Subsequent research is also underway. This is achieved through the synergistic effect of the two imunoterapija drugs to achieve the ultimate anti-tumor effect. It is expected that there will be better clinical results.
