Kulkarni Anand V, Krishna Vamsi, Kumar Karan, Sharma Mithun, Patodiya Bharat, Khan Arif, Shaik Sameer, Pasumarthy Ashirwad, Chhabra Prateek, Kumar Da Pramod, Saraswat Vivek A, Rao Padaki N, Reddy Duvvur N
Department of Hepatology and Liver Transplantation, AIG Hospitals, Hyderabad India.
Department of Oncology, AIG Hospitals, Hyderabad India.
J Clin Exp Hepatol. 2023 Jul-Aug;13(4):618-623. doi: 10.1016/j.jceh.2023.02.003. Epub 2023 Feb 10.
Atezolizumab-bevacizumab (atezo/bev) combination is a recommended first-line systemic therapy for unresectable hepatocellular carcinoma (uHCC). There are no studies from India reporting the safety and efficacy of this drug in real-world settings where most patients present in an advanced stage.
In this retrospective study from two centers in India, we included patients with uHCC who received atezo/bev as first-line systemic therapy. Comparison of overall survival (OS) among the different Child-Turcotte-Pugh (CTP) classes was the primary objective, while progression-free survival (PFS), radiologic response, and adverse events to the therapy were secondary objectives.
The median age of the 67 patients who received atezo/bev therapy was 61 (29-82) years, and 86% were males. Nonalcoholic steatohepatitis (55.2%) was the commonest cause of cirrhosis, and most patients belonged to BCLC-C (74.6%%). There were 24 patients in CTP A, 36 in CTP B, and 7 in CTP C. The median OS was 12 (95%CI, 8.16-15.83) months in the cohort. The median OS in CTP class A, B, and C was 21 (95%CI, 0-42.06) months, 9 (95%CI, 5.46-12.53) months, and 4 (95%CI, 2.14-5.85) months, respectively ( < 0.001). The median PFS in the whole cohort was 8 (95%CI, 6.03-9.96) months. The median PFS in Child A, B, and C was 18 (95%CI, 0.16-35.84) months, 8 (95%CI, 6.14-9.85) months, and 2 (95%CI, 1.77-2.23) months ( < 0.001). On mRECIST evaluation, 12.9% had achieved a complete response, 25.8% had a partial response, 27.41% had stable disease, and the rest had progressed. The objective response rate was 38.7%, and the disease control rate was 66.12%. Of the 64% who developed adverse events, 13.43% discontinued the drug. The incidence of grade ≥3 events was significantly higher in CTP C (85.7%) compared to CTP A (12.5%) and CTP B (14%) ( < 0.001).
Atezolizumab-bevacizumab is safe and effective in uHCC in real-world settings. Candidate selection is of utmost importance in treating uHCC with atezolizumab-bevacizumab to achieve a good response. Current evidence strongly suggests limited use of atezolizumab-bevacizumab in patients with CTP C, and such individuals should not be considered for this combination therapy.
阿替利珠单抗-贝伐珠单抗（阿替利珠单抗/贝伐珠单抗）联合疗法是不可切除肝细胞癌（uHCC）推荐的一线全身治疗方案。在印度，尚无研究报道该药物在大多数患者处于晚期的真实世界环境中的安全性和疗效。
在这项来自印度两个中心的回顾性研究中，我们纳入了接受阿替利珠单抗/贝伐珠单抗作为一线全身治疗的uHCC患者。比较不同Child-Turcotte-Pugh（CTP）分级的总生存期（OS）是主要目标，而无进展生存期（PFS）、影像学反应和治疗的不良事件是次要目标。
接受阿替利珠单抗/贝伐珠单抗治疗的67例患者的中位年龄为61岁（29 - 82岁），86%为男性。非酒精性脂肪性肝炎（55.2%）是肝硬化最常见的病因，大多数患者属于BCLC-C期（74.6%）。CTP A级有24例患者，CTP B级有36例，CTP C级有7例。该队列的中位OS为12个月（95%CI，8.16 - 15.83）。CTP A级、B级和C级的中位OS分别为21个月（95%CI，0 - 42.06）、9个月（95%CI，5.46 - 12.53）和4个月（95%CI，2.14 - 5.85）（P<0.001）。整个队列的中位PFS为8个月（95%CI，6.03 - 9.96）。Child A级、B级和C级的中位PFS分别为18个月（95%CI，0.16 - 35.84）、8个月（95%CI，6.14 - 9.85）和2个月（95%CI，1.77 - 2.23）（P<0.001）。根据改良RECIST评估，12.9%达到完全缓解，25.8%部分缓解，27.41%疾病稳定，其余病情进展。客观缓解率为38.7%，疾病控制率为66.12%。在出现不良事件的64%患者中，13.43%停药。CTP C级≥3级事件的发生率（85.7%）显著高于CTP A级（12.5%）和CTP B级（14%）（P<0.001）。
在真实世界环境中，阿替利珠单抗-贝伐珠单抗治疗uHCC安全有效。在使用阿替利珠单抗-贝伐珠单抗治疗uHCC时，候选患者的选择对于获得良好反应至关重要。目前的证据强烈表明，CTP C级患者使用阿替利珠单抗-贝伐珠单抗的情况有限，此类患者不应考虑这种联合治疗。
