Wang Yilin, Pan Shida, Tian Jiahe, Wang Jianing, Yu Yingying, Wang Siyu, Li Fengyi, Yang Luo, Liu Xiaomeng, Shen Yingjuan, Qiu Qin, Luan Junqing, Jia Mengdie, Xiong Chuyue, Duan Xuanxuan, Wang Fu-Sheng, Meng Fanping
Medical School of Chinese PLA, No. 28, Fuxing Road, Beijing, 100853, China.
Department of Infectious Diseases, The Fifth Medical Centre of Chinese PLA General Hospital, National Clinical Research Centre for Infectious Diseases, Beijing, 100853, China.
Cancer Immunol Immunother. 2025 Apr 28;74(6):186. doi: 10.1007/s00262-025-04038-8.
This study retrospectively evaluated the safety and efficacy of cadonilimab combined with tyrosine kinase inhibitors (TKI) for the treatment of unresectable hepatocellular carcinoma (uHCC).
Seventy-eight patients who received cadonilimab + TKI were included; 42 and 36 received it as first-line (1 L) and second-line and above (≥ 2 L) systemic treatment, respectively. Besides, ninety-five patients who received PD-1 inhibitor + TKI as first-line treatments were included. Safety was the primary endpoint; secondary endpoints were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR).
Treatment-related adverse events (TRAEs) of any grade occurred in 84.6% of the patients, with grade ≥ 3 in 20.5%. In patients with a Child-Pugh score of ≥ 8 (CP ≥ 8), any grade TRAEs occurred in 88.2%, and grade ≥ 3 in 20.6%. The overall cohort's median progression-free survival (mPFS) was 3.6 months, whereas the median overall survival (mOS) was 8.8 months. In the 1 L group, mPFS was 6.7 months versus 2.3 months in ≥ 2 L. In the 1 L group, mOS was 13.7 months versus 3.2 months in ≥ 2 L. For CP < 8, 1 L mPFS was 7.6 months, mOS not reached; CP ≥ 8 had mPFS of 5.2 months, mOS of 5.6 months. For CP < 8 in ≥ 2 L, mPFS was 3.1 months, mOS 8.8 months; CP ≥ 8 had mPFS of 1.4 months, mOS of 2.2 months. After propensity score matching (PSM), the incidence of TRAEs of any grade was 77.1%, with grade ≥ 3 accounting for 17.1% in the PD-1 group. In the PD-1/CTLA-4 group, the incidence of TRAEs of any grade was 80.0%, and that of grade ≥ 3 TRAEs was 17.1%. The mPFS was 6.7 months in the PD-1/CTLA-4 group versus 3.3 months in the PD-1 group. The mOS was 13.7 months in the PD-1/CTLA-4 group versus 6.7 months in the PD-1 group.
Cadonilimab + TKI showed a favorable trend in safety and efficacy, especially when applied as first-line systemic therapy for uHCC. This study offers a clinical reference for its use in systemic uHCC therapy, particularly in patients with advanced liver dysfunction.
本研究回顾性评估卡度尼利单抗联合酪氨酸激酶抑制剂（TKI）治疗不可切除肝细胞癌（uHCC）的安全性和有效性。
纳入78例接受卡度尼利单抗+TKI治疗的患者；其中42例和36例分别接受其作为一线（1L）和二线及以上（≥2L）全身治疗。此外，纳入95例接受PD-1抑制剂+TKI作为一线治疗的患者。安全性为主要终点；次要终点为总生存期（OS）、无进展生存期（PFS）、客观缓解率（ORR）和疾病控制率（DCR）。
84.6%的患者发生任何级别的治疗相关不良事件（TRAEs），20.5%的患者发生≥3级TRAEs。在Child-Pugh评分≥8（CP≥8）的患者中，任何级别的TRAEs发生率为88.2%，≥3级为20.6%。整个队列的中位无进展生存期（mPFS）为3.6个月，而中位总生存期（mOS）为8.8个月。在1L组中，mPFS为6.7个月，而≥2L组为2.3个月。在1L组中，mOS为13.7个月，而≥2L组为3.2个月。对于CP<8，1L的mPFS为7.6个月，mOS未达到；CP≥8的mPFS为5.2个月，mOS为5.6个月。对于≥2L且CP<8的患者，mPFS为3.1个月，mOS为8.8个月；CP≥8的mPFS为1.4个月，mOS为2.2个月。倾向评分匹配（PSM）后，PD-1组中任何级别的TRAEs发生率为77.1%，≥3级占17.1%。在PD-1/CTLA-4组中，任何级别的TRAEs发生率为80.0%，≥3级TRAEs的发生率为17.
