For patients with unresectable hepatocellular carcinoma (HCC), the first-line treatment options are limited, including local ablation, arterial-directed therapy, or external radiation therapy or chemotherapy. Sorafenib (Dogime) is currently the only approved system for patients with unresectable HCC. Sexual treatment plan. In 2017, the FDA approved regorafenib (Stivarga) and nivolumab (Opdivo) as second-line treatment options for patients who previously received sorafenib. The researchers believe that the combination of PD-L1 inhibitor durvalumab (Imfinzi) and CTLA-4 inhibitor tremelimumab may be the most appropriate clinical treatment combination.
A randomized, multicenter, phase III HIMALAYA trial (NCT03298451) divided previously untreated, unresectable HCC patients into four groups: 2 different durvalumab combined with tremelimumab combined treatment regimens, durvalumab monotherapy and sorafenib Monotherapy (picture). The researchers used overall survival (OS) as the primary endpoint and time to progression, progression-free survival (PFS), and objective response rate (ORR) as the secondary endpoints.
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 immunotherapy drugs to achieve the ultimate anti-tumor effect. It is expected that there will be better clinical results.
