Para sa mga pasyenteng hindi nareresect hepatocellular carcinoma (HCC), limitado ang mga opsyon sa first-line na paggamot, kabilang ang lokal na ablation, arterial-directed therapy, o external radiation therapy o chemotherapy. Ang Sorafenib (Dogime) ay kasalukuyang ang tanging aprubadong sistema para sa mga pasyenteng may hindi nareresect na HCC. Plano ng sekswal na paggamot. Noong 2017, inaprubahan ng FDA ang regorafenib (Stivarga) at nivolumab (Opdivo) bilang pangalawang linya ng mga opsyon sa paggamot para sa mga pasyenteng dating nakatanggap ng sorafenib. Naniniwala ang mga mananaliksik na ang kumbinasyon ng Inhibitor ng PD-L1 Ang durvalumab (Imfinzi) at CTLA-4 inhibitor na tremelimumab ay maaaring ang pinakaangkop na kumbinasyon ng klinikal na paggamot.
Isang randomized, multicenter, phase III na pagsubok sa HIMALAYA (NCT03298451) na hinati ang dati nang hindi ginagamot, hindi nareresect na mga pasyente ng HCC sa apat na grupo: 2 magkakaibang durvalumab na sinamahan ng tremelimumab na pinagsamang mga regimen sa paggamot, durvalumab monotherapy at sorafenib Monotherapy (larawan). Ginamit ng mga mananaliksik ang overall survival (OS) bilang pangunahing endpoint at oras sa pag-unlad, progression-free survival (PFS), at objective response rate (ORR) bilang pangalawang endpoint.
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 pamamaga 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 immunotherapy drugs to achieve the ultimate anti-tumor effect. It is expected that there will be better clinical results.
