Kune varwere vane unresctable hepatocellular carcinoma (HCC), nzira dzekutanga dzekurapa dzakaganhurirwa, kusanganisira kubviswa kwenzvimbo, arterial-directed therapy, kana yekunze radiation therapy kana chemotherapy. Sorafenib (Dogime) parizvino ndiyo yega system yakatenderwa yevarwere vane HCC isingagadzirisike. Chirongwa chekurapa pabonde. Muna 2017, FDA yakabvumira regorafenib (Stivarga) uye nivolumab (Opdivo) senzira dzechipiri dzekurapa kune varwere vakambogamuchira sorafenib. Vatsvakurudzi vanotenda kuti kusanganiswa kwe PD-L1 inhibitor durvalumab (Imfinzi) uye CTLA-4 inhibitor tremelimumab inogona kunge yakanyanya kukodzera kurapwa kwekiriniki musanganiswa.
A randomized, multicenter, phase III HIMALAYA muedzo (NCT03298451) yakakamura varwere veHCC vasati varapwa, vasingagadziriswi mumapoka mana: 2 yakasiyana-siyana durvalumab yakasanganiswa ne tremelimumab yakasanganiswa mishonga yekurapa, durvalumab monotherapy uye sorafenib Monotherapy (mufananidzo). Vatsvagiri vakashandisa kupona kwese (OS) seyekutanga magumo uye nguva yekufambira mberi, kufambira mberi-kusina kupona (PFS), uye chinangwa chekupindura mwero (ORR) seyechipiri magumo.
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 tumarara 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.
