Fulgenzi Claudia Angela Maria, Scheiner Bernhard, Korolewicz James, Stikas Charalampos-Vlasios, Gennari Alessandra, Vincenzi Bruno, Openshaw Mark R, Silletta Marianna, Pinter Matthias, Cortellini Alessio, Scotti Lorenza, D'Alessio Antonio, Pinato David J
Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK.
Medical Oncology Department, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy.
JHEP Rep. 2023 Feb 18;5(5):100702. doi: 10.1016/j.jhepr.2023.100702. eCollection 2023 May.
BACKGROUND & AIMS: Direct comparisons across first-line regimens for advanced hepatocellular carcinoma are not available. We performed a network metanalysis of phase III of trials to compare first-line systemic treatments for hepatocellular carcinoma in terms of overall survival (OS), progression-free survival (PFS), objective response rate, disease control rate, and incidence of adverse events (AEs).
After performing a literature review from January 2008 to September 2022, we screened 6,329 studies and reviewed 3,009 studies, leading to identification of 15 phase III trials for analysis. We extracted odds ratios for objective response rate and disease control rate, relative risks for AEs, and hazard ratios (HRs) with 95% CIs for OS and PFS, and used a frequentist network metanalysis, with fixed-effect multivariable meta-regression models to estimate the indirect pooled HRs, odds ratios, relative risks, and corresponding 95% CIs, considering sorafenib as reference.
Of 10,820 included patients, 10,444 received active treatment and 376 placebo. Sintilimab + IBI350, camrelizumab + rivoceranib, and atezolizumab + bevacizumab provided the greatest reduction in the risk of death compared with sorafenib, with HRs of 0.57 (95% CI 0.43-0.75), 0.62 (95% CI 0.49-0.79), and 0.66 (95% CI 0.52-0.84), respectively. Considering PFS, camrelizumab + rivoceranib and pembrolizumab + lenvatinib were associated with the greatest reduction in the risk of PFS events compared with sorafenib, with HRs of 0.52 (95% CI 0.41-0.65) and 0.52 (95% CI 0.35-0.77), respectively. Immune checkpoint inhibitor (ICI) monotherapies carried the lowest risk for all-grade and grade ≥3 AEs.
The combinations of ICI + anti-vascular endothelial growth factor, and double ICIs lead to the greatest OS benefit compared with sorafenib, whereas ICI + kinase inhibitor regimens are associated with greater PFS benefit at the cost of higher toxicity rates.
In the last few years, many different therapies have been studied for patients with primary liver cancer that cannot be treated with surgery. In these cases, anticancer drugs (alone or in combination) are given with the intent to keep the cancer at bay and, ultimately, to prolong survival. Among all the therapies that have been investigated, the combination of immunotherapy (drugs that boost the immune system against the cancer) and anti-angiogenic agents (drugs that act on tumoural vessels) has appeared the best to improve survival. Similarly, the combination of two types of immunotherapies that activate the immune system at different levels has also shown positive results.
PROSPERO CRD42022366330.
目前尚无针对晚期肝细胞癌一线治疗方案的直接比较。我们对III期试验进行了网状荟萃分析，以比较肝细胞癌一线全身治疗在总生存期（OS）、无进展生存期（PFS）、客观缓解率、疾病控制率和不良事件（AE）发生率方面的差异。
在对2008年1月至2022年9月的文献进行回顾后，我们筛选了6329项研究并审查了3009项研究，最终确定了15项III期试验进行分析。我们提取了客观缓解率和疾病控制率的比值比、AE的相对风险以及OS和PFS的风险比（HRs）及其95%置信区间（CIs），并使用频率学派网状荟萃分析，采用固定效应多变量Meta回归模型来估计间接合并HRs、比值比、相对风险以及相应的95% CIs，以索拉非尼作为对照。
在纳入的10820例患者中，10444例接受了积极治疗，376例接受了安慰剂治疗。与索拉非尼相比，信迪利单抗+IBI350、卡瑞利珠单抗+瑞戈非尼以及阿替利珠单抗+贝伐单抗降低死亡风险的效果最为显著，HRs分别为0.57（95% CI 0.43 - 0.75）、0.62（95% CI 0.49 - 0.79）和0.66（95% CI 0.52 - 0.84）。考虑PFS时，与索拉非尼相比，卡瑞利珠单抗+瑞戈非尼以及帕博利珠单抗+仑伐替尼降低PFS事件风险的效果最为显著，HRs分别为0.52（95% CI 0.41 - 0.65）和0.52（95% CI 0.35 - 0.77）。免疫检查点抑制剂（ICI）单药治疗的所有级别和≥3级AE风险最低。
与索拉非尼相比，ICI + 抗血管内皮生长因子以及双联ICI联合方案带来的OS获益最大，而ICI + 激酶抑制剂方案虽与更大的PFS获益相关，但毒性发生率更高。
在过去几年中，针对无法手术治疗的原发性肝癌患者研究了许多不同的治疗方法。在这些情况下，给予抗癌药物（单独或联合使用）旨在控制癌症并最终延长生存期。在所有已研究的治疗方法中，免疫疗法（增强免疫系统对抗癌症的药物）和抗血管生成药物（作用于肿瘤血管的药物）联合使用似乎最有利于提高生存期。同样，在不同水平激活免疫系统的两种免疫疗法联合使用也显示出了积极的效果。
PROSPERO CRD42022366330
