Sintilimab plus a Bevacizumab biosimilar (IBI305) in Advanced HCC with Child-Pugh A/B liver function: A Real-World Multicenter Retrospective Study

Yuanxu Zhang¹Youhan Miao²Wei Sun¹Yixing Yu¹Jinjing Wang¹Shuang Xiao¹Shengwei Lu¹Xia Wang³Zhao Weifeng^1*Yang Li^4*Xiucheng Pan^3*

• ¹First Affiliated Hospital of Soochow University, Suzhou, China
• ²The Third People's Hospital of Nantong, Nantong, China
• ³The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
• ⁴The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, China

1 Background: Sintilimab plus a Bevacizumab biosimilar (IBI305) is an approved first-line 2 regimen for unresectable hepatocellular carcinoma (uHCC) in China. However, data on its 3 safety and efficacy in patients with impaired liver function remain limited. We assessed the 4 clinical outcomes of this combination therapy in HCC patients with Child-Pugh class A (CP-5 A) and class B (CP-B) liver function. 6 Methods: In this multicentre retrospective cohort study, 99 patients with advanced uHCC (73 7 CP-A; 26 CP-B) who received first-line Sin/Bev were included. Tumor response was assessed 8 using modified RECIST criteria, and adverse events (AEs) were graded per CTCAE v5.0. 9 Survival outcomes, including overall survival (OS), progression-free survival (PFS), and time 10 to hepatic decompensation (TTD), were analyzed via Kaplan-Meier estimates and Cox 11 proportional hazards models. 12 Results: The objective response rates (ORR) of patients with CP-A and CP-B treated with 13 Sin/Bev were 50.7% and 57.7%, respectively, and both could achieve good anti-tumor 14 efficacy. CP-B had inferior survival: median OS (15 vs 22 months, p=0.044), PFS (8 vs 14 15 months, p=0.014), and TTD (7 vs 15 months, p<0.001). The CP-B cohort demonstrated 16 comparable incidence rates of grade 3-4 AEs to the CP-A group (34.6% vs 34.2%). 17 Hemorrhagic events and thrombocytopenia emerged as predominant grade 3-4 AEs in CP-B 18 patients (15.4% for both). 19 Conclusions: Sin/Bev demonstrated encouraging short-term anti-tumor activity in HCC of 20 CP-A and CP-B, while survival outcomes were affected by differences in hepatic function. 21 Although the regimen was generally well tolerated, patients with impaired liver reserve 22 require vigilant monitoring and comprehensive supportive strategies to maximize therapeutic 23 outcomes.