Updated results from venous infusion chemotherapy (VIC) plus apatinib and camrelizumab for hepatocellular carcinoma (HCC) in CNLC stage III: A prospective, single-arm, phase II trial.
Authors: Peng Linhui , Chen Tao , Chen Yajin , Yunxiuxiu Xu , Wang Jie , Chen Jie , Li Yong , Huang Pinbo , Hu Xiao , Zhong Guoping , Chen Xi , Ye Congting 
Published: June 2024

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Background: Recently, hepatic artery infusion chemotherapy (HAIC) plus antiangiogenic drugs and PD-(L)1 inhibitors has been widely used in advanced HCC and improved the prognosis of HCC in China. But HAIC has disadvantages such as invasive operation, technical limitations, expensive cost and poor patient comfort. This study aimed to investigate the efficacy and safety of VIC plus apatinib and camrelizumab for CNLC stage Ⅲ HCC. Methods: This single-arm, phase II study included treatment-naive adult patients (pts) with CNLC stage Ⅲ and Child-Pugh score A or B (NCT05412589). Eligible pts were administered VIC (oxaliplatin 85 mg/m2, leucovorin 200 mg/m2, 5-fluorouracil bolus 400 mg/m2 on day 1, and 5-fluorouracil infusion 2400 mg/m2 for 46 hours; q3w; 6 cycles), plus apatinib (250 mg qd) and camrelizumab (200 mg q3w) until disease progression or intolerable toxicity occurred. The primary endpoint was objective response rate (ORR) evaluated by RECIST 1.1. Secondary endpoints were overall survival (OS), progression-free survival (PFS) per RECIST 1.1 or mRECIST and safety. Using the Simon optimal 2 stage design, the planned sample size is 34 evaluable pts with 85% power and alpha of 5% to detect an increase in ORR from 25% to 55%. Interim analysis requiring at least 3 confirmed responses in the first 10 pts to proceed to full accrual. Results: 35 pts were enrolled (2 woman and 33 men; median age, 48 years; 34 had HBV infection). The median tumor size was 103mm. 23 (65.7%) pts had more than 2 tumors. 12 (34.3%) pts had main portal trunk invasion (Vp4); 22 (62.9%) pts had distant metastasis. The median follow-up was 9.7 months and all pts had at least one post-baseline tumor assessment. The confirmed ORR was 60.0% (21/35, 95% CI, 42.9-77.1) per RECIST 1.1, while 68.6% (24/35,95% CI, 52.4- 84.8) per mRECIST. 21(60.0%) pts received operation successfully and 8 (38.1%) pts reached pathological complete response. In particular, the 12 VP4 pts were equally effective, with ORR of 66.7% (RECIST 1.1) and 83.3% (mRECIST). The disease control rate was 97.1% (95% CI, 91.3-102.9) per RECIST 1.1 or mRECIST. The estimated 6- and 9-month PFS rate was 93.6% (95% CI, 76.8-98.4) and 81.5% (95% CI, 60.5-92.0) per RECIST 1.1. The 6- and 9-month OS rate were 100% and 95.7% (95% CI, 72.9-99.4). Grade 3-4 treatment-related AEs occurred in 40% of patients, of which the most common were diarrhea (23.9%) , thrombocytopenia (25.9%), and hypertension (11.1%). All AEs were expected and manageable, and no treatment-related deaths were reported. Conclusions: In CNLC stage Ⅲ HCC, the new VIC-triplet treatment system demonstrated acceptable safety and the same anti-tumor effects as HAIC plus antiangiogenic drugs and PD-(L)1 inhibitors, especially in those with VP4. These findings provided new insights for treatment of advanced HCC and a relevant clinical phase 3 study was underway. Clinical trial information: NCT05412589 .