Yuan Guosheng, Chen Yongru, Zhu Peilin, Deng Qiong, Su Kaiyan, Liu Jie, Wang Yan, Li Rong, Li Wenli, Zang Mengya, Hu Xiaoyun, Wang Jun-Jie, Li Qi, Du Yangfeng, Chen Jinzhang
State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
Heliyon. 2024 Sep 16;10(19):e37616. doi: 10.1016/j.heliyon.2024.e37616. eCollection 2024 Oct 15.
Previous research has shown that combining tyrosine kinase inhibitors (TKIs) with immunotherapy results in synergistic clinical efficacy. Cadonilimab, the first approved bi-specific antibody targeting PD-1 and CTLA-4, was studied to evaluate its efficacy and safety in combination with Lenvatinib as a first-line treatment for patients with unresectable hepatocellular carcinoma (uHCC).
A retrospective study was conducted on 29 uHCC patients diagnosed at Nanfang Hospital, Southern Medical University, between July 7, 2022, and March 3, 2023. Patients received Cadonilimab (10 mg/kg, IV, every 3 weeks) combined with Lenvatinib (8 mg, orally, daily). The primary endpoint was the objective response rate (ORR), with secondary endpoints including disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS), median time to progression (mTTP), and safety.
By April 2023, 29 patients had been enrolled in the study. The ORR was 37.9 %, DCR was 82.8 %, mPFS was 8.1 months, mTTP was 8.2 months, and mOS was not reached. A total of 93.1 % of patients experienced at least one treatment-related adverse event (TRAE). The most common adverse events were weight loss (51.7 %), increased aspartate aminotransferase (48.3 %), leukocytopenia (48.3 %), and neutropenia (48.3 %). TRAEs of grade 3 or higher occurred in 51.7 % of patients, with no grade 4 TRAEs observed.
This study demonstrated the efficacy and safety of this combination, potentially improving outcomes as a first-line therapy, and offering a novel therapeutic approach for advanced HCC.
先前的研究表明，酪氨酸激酶抑制剂（TKIs）与免疫疗法联合使用可产生协同临床疗效。对首个获批的靶向PD-1和CTLA-4的双特异性抗体卡度尼利单抗进行了研究，以评估其与乐伐替尼联合用于不可切除肝细胞癌（uHCC）患者一线治疗的疗效和安全性。
对2022年7月7日至2023年3月3日期间在南方医科大学南方医院确诊的29例uHCC患者进行了一项回顾性研究。患者接受卡度尼利单抗（10mg/kg，静脉注射，每3周一次）联合乐伐替尼（8mg，口服，每日一次）治疗。主要终点是客观缓解率（ORR），次要终点包括疾病控制率（DCR）、无进展生存期中位数（mPFS）、总生存期中位数（mOS）、疾病进展时间中位数（mTTP）和安全性。
截至2023年4月，29例患者纳入研究。ORR为37.9%，DCR为82.8%，mPFS为8.1个月，mTTP为8.2个月，mOS未达到。共有93.1%的患者经历了至少一次治疗相关不良事件（TRAE）。最常见的不良事件是体重减轻（51.7%）、天冬氨酸转氨酶升高（48.3%）、白细胞减少（48.3%）和中性粒细胞减少（48.3%）。51.7%的患者发生3级或更高等级的TRAE，未观察到4级TRAE。
本研究证明了该联合治疗的疗效和安全性，可能改善一线治疗结局，并为晚期肝癌提供一种新的治疗方法。
