Piscaglia F, Masi G, Martinelli E, Cabibbo G, Di Maio M, Gasbarrini A, Iavarone M, Antonuzzo L, Mazzaferro V, Ballestrero A, Garufi C, Bergamo F, Celsa C, Marino D, Tovoli F, Ponziani F R, Pressiani T, Astolfi C, Gazzoli G C, Ciardiello F, Daniele B, Rimassa L
Division of Internal Medicine, Hepatobiliary and Immunoallergic Disease, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
ESMO Open. 2025 Feb;10(2):104110. doi: 10.1016/j.esmoop.2024.104110. Epub 2025 Jan 27.
The treatment of advanced hepatocellular carcinoma (HCC) with atezolizumab and bevacizumab led to significant improvements in overall survival (OS), progression-free survival (PFS), and response rate compared with sorafenib in the phase III IMbrave150 trial. The etiology of background liver disease can differ between Eastern and Western populations, leading to a potentially different impact of systemic therapies; therefore the unequal representation must be considered in the IMbrave150 trial. To provide further data on the safety and effectiveness of atezolizumab and bevacizumab, the phase IIIb AMETHISTA (Atezolizumab plus bevacizumab in METastatic HCC Italian Safety TriAl) ran in a Western (Italian) population of patients with advanced HCC. The results of the interim analysis are presented in this paper.
AMETHISTA is a multicenter, phase IIIb, single-arm study evaluating the safety and effectiveness of atezolizumab and bevacizumab in an Italian population of patients with systemic treatment-naive HCC (ClinicalTrials.gov: NCT04487067). The primary objective was safety (incidence of grade 3-5 bleeding/hemorrhages). The main secondary objective was effectiveness.
A total of 152 patients were enrolled and 149 were treated. At the cut-off date, the median observation time was 13.4 months (interquartile range 8.3-15.5 months). The incidence of grade 3-5 bleeding/hemorrhages was 11.4%. Besides, results of other safety endpoints were consistent with the safety profile of atezolizumab plus bevacizumab, and the underlying disease, without any new safety observation. The median OS was 18.2 months (95% confidence interval 15.4 months to not evaluable); the median PFS was 8.5 months (95% confidence interval 7.5-11.2 months).
Results from the interim analysis are consistent with data from the IMbrave150 trial, and further confirm first-line atezolizumab plus bevacizumab as a standard of care for patients with systemic treatment-naive advanced and unresectable HCC.
在III期IMbrave150试验中，与索拉非尼相比，阿替利珠单抗联合贝伐单抗治疗晚期肝细胞癌（HCC）可显著改善总生存期（OS）、无进展生存期（PFS）和缓解率。东西方人群背景肝病的病因可能不同，导致全身治疗的影响可能存在差异；因此，在IMbrave150试验中必须考虑代表性不均衡的问题。为了提供关于阿替利珠单抗和贝伐单抗安全性和有效性的更多数据，IIIb期AMETHISTA（阿替利珠单抗联合贝伐单抗治疗转移性HCC的意大利安全性试验）在西方（意大利）晚期HCC患者人群中开展。本文展示了中期分析结果。
AMETHISTA是一项多中心、IIIb期、单臂研究，评估阿替利珠单抗和贝伐单抗在未接受过全身治疗的意大利HCC患者人群中的安全性和有效性（ClinicalTrials.gov：NCT04487067）。主要目标是安全性（3 - 5级出血/出血事件的发生率）。主要次要目标是有效性。
共纳入152例患者，149例接受治疗。截止日期时，中位观察时间为13.4个月（四分位间距8.3 - 15.5个月）。3 - 5级出血/出血事件的发生率为11.4%。此外，其他安全性终点结果与阿替利珠单抗联合贝伐单抗的安全性特征以及基础疾病一致，未出现任何新的安全性观察结果。中位OS为18.2个月（95%置信区间15.4个月至不可评估）；中位PFS为8.5个月（95%置信区间7.5 - 11.2个月）。
中期分析结果与IMbrave150试验数据一致，并进一步证实一线阿替利珠单抗联合贝伐单抗是未接受过全身治疗的晚期不可切除HCC患者的标准治疗方案。
