Til patienter med uoperable hepatocellulært karcinom (HCC), er førstelinjebehandlingsmulighederne begrænsede, herunder lokal ablation, arteriel rettet terapi eller ekstern strålebehandling eller kemoterapi. Sorafenib (Dogime) er i øjeblikket det eneste godkendte system til patienter med uoperabelt HCC. Seksuel behandlingsplan. I 2017 godkendte FDA regorafenib (Stivarga) og nivolumab (Opdivo) som andenlinjebehandlingsmuligheder for patienter, der tidligere fik sorafenib. Forskerne mener, at kombinationen af PD-L1 hæmmer durvalumab (Imfinzi) og CTLA-4-hæmmer tremelimumab kan være den mest passende kliniske behandlingskombination.
Et randomiseret, multicenter, fase III HIMALAYA-forsøg (NCT03298451) inddelte tidligere ubehandlede, ikke-operable HCC-patienter i fire grupper: 2 forskellige durvalumab kombineret med tremelimumab kombinerede behandlingsregimer, durvalumab monoterapi og sorafenib Monoterapi (billede). Forskerne brugte samlet overlevelse (OS) som det primære endepunkt og tid til progression, progressionsfri overlevelse (PFS) og objektiv responsrate (ORR) som sekundære endepunkter.
Durvaluumab 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 immunterapi drugs to achieve the ultimate anti-tumor effect. It is expected that there will be better clinical results.
