Department of Radiology, University Hospital, LMU Munich, Munich, Germany.
Department of Medical Oncology, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, Amsterdam, the Netherlands.
J Hepatol. 2019 Dec;71(6):1164-1174. doi: 10.1016/j.jhep.2019.08.006. Epub 2019 Aug 14.
BACKGROUND & AIMS: Sorafenib is the recommended treatment for patients with advanced hepatocellular carcinoma (HCC). We aimed to compare the efficacy and safety of a combination of sorafenib and selective internal radiation therapy (SIRT) - with yttrium-90 (Y) resin microspheres - to sorafenib alone in patients with advanced HCC.
SORAMIC is a randomised controlled trial comprising diagnostic, local ablation and palliative cohorts. Based on diagnostic study results, patients were assigned to local ablation or palliative cohorts. In the palliative cohort, patients not eligible for TACE were randomised 11:10 to SIRT plus sorafenib (SIRT + sorafenib) or sorafenib alone. The primary endpoint was overall survival (OS; Kaplan-Meier analysis) in the intention-to-treat (ITT) population.
In the ITT cohort, 216 patients were randomised to SIRT + sorafenib and 208 to sorafenib alone. Median OS was 12.1 months in the SIRT + sorafenib arm, and 11.4 months in the sorafenib arm (hazard ratio [HR] 1.01; 95% CI 0.81-1.25; p = 0.9529). Median OS in the per protocol population was 14.0 months in the SIRT + sorafenib arm (n = 114), and 11.1 months in the sorafenib arm (n = 174; HR 0.86; p = 0.2515). Subgroup analyses of the per protocol population indicated a survival benefit of SIRT + sorafenib for patients without cirrhosis (HR 0.46; 0.25-0.86; p = 0.02); cirrhosis of non-alcoholic aetiology (HR 0.63; p = 0.012); or patients ≤65 years old (HR 0.65; p = 0.05). Adverse events (AEs) of Common Terminology Criteria for AE Grades 3-4 were reported in 103/159 (64.8%) patients who received SIRT + sorafenib, 106/197 (53.8%) patients who received sorafenib alone (p = 0.04), and 8/24 (33.3%) patients who only received SIRT.
Addition of SIRT to sorafenib did not result in a significant improvement in OS compared with sorafenib alone. Subgroup analyses led to hypothesis-generating results that will support the design of future studies.
Sorafenib given orally is the recommended treatment for patients with advanced hepatocellular carcinoma (HCC). In selective internal radiation therapy (SIRT), also known as radioembolisation, microscopic, radioactive resin or glass spheres are introduced into the blood vessels that feed the tumours in the liver. This study found that the addition of SIRT with yttrium-loaded resin microspheres to sorafenib treatment in people with advanced HCC did not significantly improve overall survival compared with sorafenib treatment alone. However, the results give an indication of how future studies using this combination therapy in people with advanced HCC could be designed.
EudraCT 2009-012576-27, NCT0112 6645.
索拉非尼是治疗晚期肝细胞癌（HCC）的推荐药物。我们旨在比较索拉非尼联合选择性内部放射治疗（SIRT）-用钇 90（Y）树脂微球-与索拉非尼单独治疗晚期 HCC 患者的疗效和安全性。
SORAMIC 是一项随机对照试验，包括诊断、局部消融和姑息治疗队列。根据诊断研究结果，将患者分配至局部消融或姑息治疗队列。在姑息治疗队列中，不符合 TACE 标准的患者以 11:10 的比例随机分为 SIRT 联合索拉非尼（SIRT+索拉非尼）或索拉非尼单独治疗组。主要终点是意向治疗（ITT）人群的总生存期（OS；Kaplan-Meier 分析）。
在 ITT 队列中，216 例患者被随机分配至 SIRT+索拉非尼组，208 例患者被随机分配至索拉非尼单独治疗组。SIRT+索拉非尼组的中位 OS 为 12.1 个月，索拉非尼组为 11.4 个月（HR 1.01；95%CI 0.81-1.25；p=0.9529）。在方案人群中，SIRT+索拉非尼组的中位 OS 为 14.0 个月（n=114），索拉非尼组为 11.1 个月（n=174；HR 0.86；p=0.2515）。方案人群的亚组分析表明，SIRT+索拉非尼对无肝硬化（HR 0.46；0.25-0.86；p=0.02）、非酒精性病因性肝硬化（HR 0.63；p=0.012）或≤65 岁的患者（HR 0.65；p=0.05）有生存获益。SIRT+索拉非尼组有 103/159（64.8%）例患者和索拉非尼组有 106/197（53.8%）例患者报告了常见不良事件术语标准 3-4 级不良事件（p=0.04），而仅接受 SIRT 的患者有 8/24（33.3%）例患者报告了不良事件。
与单独使用索拉非尼相比，联合 SIRT 并未显著改善 OS。亚组分析得出了一些产生假设的结果，这些结果将支持未来研究的设计。
索拉非尼口服是治疗晚期肝细胞癌（HCC）的推荐方法。在选择性内部放射治疗（SIRT）中，也称为放射性栓塞，将微小的放射性树脂或玻璃微球引入到肝脏肿瘤供血的血管中。这项研究发现，与单独使用索拉非尼相比，将 SIRT 与钇负载的树脂微球联合用于治疗晚期 HCC 患者并没有显著改善总生存期。然而，这些结果表明，未来在晚期 HCC 患者中使用这种联合治疗的研究可以如何设计。
EudraCT 2009-012576-27，NCT01126645。
