Anti-PD-1 antibody SHR-1210 combined with apatinib as adjuvant treatment in patients with hepatocellular carcinoma at high risk of recurrence after radical resection: Preliminary results from a multicenter, randomized, controlled phase II trial.

Abstract

285 Background: There is no globally recognized standard adjuvant therapy for HCC after radical resection. Herein, we explored to evaluate the efficacy and safety of anti-PD-1 antibody SHR-1210 combined with apatinib as adjuvant treatment versus hepatic arterial infusion (HAI) in HCC patients with high risk of recurrence after radical resection. Methods: This was an ongoing multicencer, randomized, controlled phase 2 trial. All HCC patients were Child-Pugh Class A, and confirmed as high risk of recurrence such as portal vein tumor thrombus (PVTT) involved in second-order branch or above, microvascular invasion (MVI) and microsatellite leisions. Eligible patients were randomly assigned (1:1) to receive SHR-1210 (200mg, q2w) and apatinib (250mg, q.d.) for 12 cycles, or two times of standard HAI treatments (epirubicin 80-100mg or epirubicin 50mg+oxaliplatin 50mg). The primary endpoint was recurrence-free survival (RFS), and the secondary endpoints included safety and quality of life score (QoL). Results: From Jun 12, 2019 to Sep 15, 2020, 32 Chinese HCC patients (pts) (16pts in SHR-1210-apatinib group and HAI group, respectively) had been recruited. Full analysis (FAS) population contained 29 pts and intention to treat (ITT) population included 32 pts. The hadzard ratio for relapse or death with SHR-1210-apatinib as compared with HAI was 0.48 (95% CI 0.12-1.75; P = 0.2992) and 0.38 (95% CI 0.11-1.20; P = 0.0910) in FAS and ITT population, respectively, at date cutoff. Median RFS was not reached and 10.5 months in SHR-1210-apatinib group and HAI group, respectively. The average QoL score during treatment was 48.8 and 49.2 in SHR-1210-apatinib group and HAI group, respectively. The most common grade 3 or 4 adverse events occurred in SHR-1210-Apatinib were γ-glutamyltransferase (GGT) increase (18.75%), leukopenia (12.50%), neutrophil count decrease, alanine and aspartate aminotransferase increase (12.50%), while in HAI group were lymphocyte count decrease (7.69%), hemoglobin increase (7.69%) and GGT increase (7.69%). Conclusions: In HCC patients with high risk of recurrence after radical resection, SHR-1210 combined with apatinib was tolerable, and might offer a new promising choice superior to HAI for adjuvant therapy in HCC, further study is needed to reach the pre-defined primary endpoint. Clinical trial information: NCT03839550.