Singh Satender P, Kumar Karan, Kulkarni Anand, Arora Vinod, Choudhury Ashok, Chaubal Alisha, Rathi Sahaj, Shah Samir, Taneja Sunil, Kumar Ashish, Duseja Ajay, Kumar Guresh, Nagaraja Rao P, Saraswat Vivek, Sarin Shiv K
Department of Hepatology, Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, India.
Department of Hepatology and Liver Transplant, Mahatma Gandhi Hospital, Jaipur, India.
J Clin Exp Hepatol. 2025 Jul-Aug;15(4):102513. doi: 10.1016/j.jceh.2025.102513. Epub 2025 Feb 8.
The approved immunotherapies for patients with advanced HCC are Atezolizumab and Bevacizumab. However, patients in India present late and healthcare is often available through self-financing. To rationalise the therapy, we conducted a large multicentre study to identify the baseline predictors of non-response to atezolizumab and bevacizumab in advanced unresectable HCC.
A dose of atezolizumab 1200 mg and bevacizumab 15 mg/kg was used every 3 weeks from 6 centres across India. A total of 278 patients were screened, and 160 were included in the study. The study included patients with locally advanced metastatic or inoperable hepatocellular carcinoma who were at least 18 years of age and those who received <3 injections were excluded. Fifty-four percent of the included patients were BCLC-B and 46% were BCLC-C. The primary objective was to study overall survival and progression-free survival. While identifying radiological response, objective response rate and adverse effects were secondary objectives.
The mean age was 61.9 ± 11.7 years, 88% were male, 55% had NASH, 16.3% had hepatitis C, 18.8% had hepatitis B and the rest were alcohol. The mean Model for End-Stage Liver Disease (MELD) is 12.05 ± 4.46, Albumin-Bilirubin Score (ALBI) is -2.04 ± 0.57. Fifty-five percent received first-line and 45% as second/other line therapy. The median overall survival was 10 (95% confidence interval [CI]: 6.1-15.6) months. Progression-free survival was found to be 8 (95%CI: 5.1-14.7) months overall. Eleven (6.9%) achieved complete response, 28 (17.5%) partial response, 33 (20.6%) had stable disease and 88 (55%) had progressive disease. On multivariate analysis, CRP>1 mg/dl (-0.007), PIVKA-II>400 mAU/mL (-0.019), AFP>100 ng/ml (-0.009), presence of diabetes (-0.042) were associated with non-response to atezolizumab and bevacizumab injection. Fifty-three percent of patients developed any grade of adverse effect, and 20% developed grade 3/4 adverse events amounting to the stoppage of therapy.
Non-response to atezolizumab and bevacizumab immunotherapy was predicted by CRP>1 mg/dl, PIVKA-II>400mAU/ml, AFP>100 ng/ml and the presence of diabetes.
晚期肝细胞癌（HCC）患者获批的免疫疗法是阿替利珠单抗和贝伐单抗。然而，印度患者就诊较晚，且医疗保健通常需自费。为使治疗更合理，我们开展了一项大型多中心研究，以确定晚期不可切除HCC患者对阿替利珠单抗和贝伐单抗无反应的基线预测因素。
印度6个中心每3周使用一次剂量为1200mg的阿替利珠单抗和15mg/kg的贝伐单抗。共筛查278例患者，160例纳入研究。研究纳入年龄至少18岁、局部晚期转移性或无法手术切除的肝细胞癌患者，排除接受过<3次注射的患者。纳入患者中54%为巴塞罗那临床肝癌（BCLC）-B期，46%为BCLC-C期。主要目标是研究总生存期和无进展生存期。确定放射学反应、客观缓解率和不良反应为次要目标。
平均年龄为61.9±11.7岁，88%为男性，55%有非酒精性脂肪性肝炎（NASH），16.3%有丙型肝炎，18.8%有乙型肝炎，其余为酒精性肝炎。终末期肝病模型（MELD）平均为12.05±4.46，白蛋白-胆红素评分（ALBI）为-2.04±0.57。55%接受一线治疗，45%接受二线/其他线治疗。中位总生存期为10（95%置信区间[CI]：6.1-15.6）个月。总体无进展生存期为8（95%CI：5.1-14.7）个月。11例（6.9%）达到完全缓解，28例（17.5%）部分缓解，33例（20.6%）病情稳定，88例（55%）病情进展。多因素分析显示，C反应蛋白（CRP）>1mg/dl（-0.007）、异常凝血酶原（PIVKA-II）>400mAU/mL（-0.019）、甲胎蛋白（AFP）>100ng/ml（-0.009）、糖尿病的存在（-0.042）与对阿替利珠单抗和贝伐单抗注射无反应相关。53%的患者出现任何级别的不良反应，20%出现3/4级不良事件导致治疗中断。
CRP>1mg/dl、PIVKA-II>400mAU/ml、AFP>100ng/ml和糖尿病的存在可预测对阿替利珠单抗和贝伐单抗免疫治疗无反应。
