阿特珠单抗加贝伐单抗的获批以及喜马拉雅试验的积极结果拓宽了晚期HCC的治疗方案，同时也带来了新的挑战。首先，迫切需要用于将患者分配到最佳治疗的预测性生物标志物；其次，迫切需要具体的研究来确定新组合在通常被排除在临床试验之外的患者中的使用，例如肝功能紊乱和 HIV 或移植受者。最后，随着新组合被转化为早期阶段，辅助和新辅助设置很快就会发生深刻变化。
Novel immunotherapy combinations in clinical trials for hepatocellular carcinoma: will they shape the future treatment landscape?
Claudia Angela Maria Fulgenzi
, Antonio D’Alessio
, Olabisi Ogunbiyi
, Coskun O. Demirtas
, Alessandra Gennari
, Alessio Cortellini
, show all
Pages 681-691 | Received 18 Mar 2022, Accepted 28 Apr 2022, Accepted author version posted online: 04 May 2022, Published online: 06 May 2022
Underlying liver disease and the intrinsic chemoresistance have historically hampered the development of efficacious treatments in HCC. However, in the last few years, immunotherapy-based combinations have emerged as efficacious therapeutic strategy in this setting. This paper critically summarizes the recent therapeutic progress in the systemic treatment of HCC.
Area covered
This paper examines the preclinical rationale of the following combinations in HCC: dual checkpoint inhibitors, immune checkpoint inhibitors plus anti-angiogenic agents, and immune checkpoint inhibitors plus tyrosine kinase inhibitors. Results of recent clinical studies are presented, along with a brief overview of ongoing and future trials.
Expert opinion
The approval of atezolizumab plus bevacizumab and the positive results of the HIMALAYA trial have broadened the therapeutic scenario for advanced HCC, opening, at the same time, new challenges. First of all, predictive biomarkers to allocate patients to the best treatment are eagerly required; second, specific studies are urgently needed to define the use of new combinations in patients usually excluded from clinical trials, e.g. those with deranged liver function and HIV or transplant recipients. Finally, with new combinations being translated into earlier stages, profound changes are soon expected in the adjuvant and neoadjuvant setting.