Rimassa Lorenza, Pressiani Tiziana, Merle Philippe
Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center - IRCCS, Milan, Italy.
Hepatology Unit, Croix-Rousse Hospital, Groupement Hospitalier Lyon Nord, Lyon, France.
Liver Cancer. 2019 Nov;8(6):427-446. doi: 10.1159/000499765. Epub 2019 May 29.
Patients with advanced hepatocellular carcinoma (HCC) typically have poor survival outcomes. Until recently, sorafenib was the only systemic therapy option available and no agents were approved after sorafenib failure. However, rapid changes are beginning to emerge in the treatment landscape of advanced HCC, with approvals of regorafenib, nivolu-mab, lenvatinib, pembrolizumab, and cabozantinib and positive phase II/III clinical trial results with other agents.
Here, we provide a comprehensive overview of the clinical trial data of systemic agents that are currently approved for advanced HCC (sorafenib, regorafenib, and nivolumab), including agents recently approved in 2018 (lenvatinib, pembrolizumab, and cabozantinib) and those with recent positive phase II/III results (ramucirumab). Key features of the clinical trial design, including patient selection criteria, the use of biomarkers in HCC, and criteria for efficacy assessment, and their implications in real-world practice are discussed. Important ongoing and planned trials in advanced HCC are summarized to provide a glimpse into the future of advanced HCC treatment. From a physician's viewpoint, the treatment algorithms for advanced HCC are undergoing significant changes, as additional and imminent approvals impact the choices of first- and second-line treatment and decisions regarding the timing of therapy initiation. With these additional choices at hand, treatment sequencing remains a complex task and should take patient selection and tolerance profiles into account.
The treatment of advanced HCC remains challenging and complex. The rapid developments in systemic therapy for advanced HCC should be considered when determining the best choice and sequence of treatment for patients with advanced HCC.
晚期肝细胞癌（HCC）患者的生存预后通常较差。直到最近，索拉非尼还是唯一可用的全身治疗选择，索拉非尼治疗失败后没有其他药物获批。然而，晚期HCC的治疗格局开始迅速变化，瑞戈非尼、纳武利尤单抗、仑伐替尼、帕博利珠单抗和卡博替尼获批，其他药物也取得了积极的II/III期临床试验结果。
在此，我们全面概述了目前已获批用于晚期HCC的全身治疗药物（索拉非尼、瑞戈非尼和纳武利尤单抗）的临床试验数据，包括2018年最近获批的药物（仑伐替尼、帕博利珠单抗和卡博替尼）以及近期取得积极II/III期结果的药物（雷莫西尤单抗）。讨论了临床试验设计的关键特征，包括患者选择标准、HCC中生物标志物的使用以及疗效评估标准及其在实际临床实践中的意义。总结了晚期HCC正在进行和计划中的重要试验，以展望晚期HCC治疗的未来。从医生的角度来看，晚期HCC的治疗算法正在发生重大变化，因为更多即将获批的药物影响一线和二线治疗的选择以及治疗开始时机的决策。有了这些额外的选择，治疗顺序仍然是一项复杂的任务，应考虑患者的选择和耐受情况。
晚期HCC的治疗仍然具有挑战性且复杂。在为晚期HCC患者确定最佳治疗选择和顺序时，应考虑晚期HCC全身治疗的快速发展。
