美法仑隔离肝灌注治疗葡萄膜黑色素瘤肝转移后的生存情况和生活质量——III期随机对照试验SCANDIUM的最终结果

Survival and Quality of Life after Isolated Hepatic Perfusion with Melphalan as a Treatment for Uveal Melanoma Liver Metastases - Final Results from the Phase III Randomized Controlled Trial SCANDIUM.

作者信息

Olofsson Bagge Roger, Nelson Axel, Shafazand Amir, All-Eriksson Charlotta, Cahlin Christian, Elander Nils, Gustavsson Anders, Helgadottir Hildur, Kiilgaard Jens Folke, Kinhult Sara, Ljuslinder Ingrid, Mattsson Jan, Rizell Magnus, Sternby Eilard Malin, Ullenhag Gustav J, Nilsson Jonas A, Ny Lars, Lindnér Per

机构信息

Sahlgrenska Center for Cancer Research, Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden.

出版信息

Ann Surg. 2024 Feb 29. doi: 10.1097/SLA.0000000000006255.

DOI:10.1097/SLA.0000000000006255

PMID:38420778

Abstract

OBJECTIVE

To investigate overall survival (OS) and health-related quality of life (HRQOL) of first-line isolated hepatic perfusion (IHP) compared to best alternative care (BAC) for patients with uveal melanoma liver metastases.

SUMMARY BACKGROUND DATA

Approximately half of patients with uveal melanoma develop metastatic disease, most commonly in the liver and systemic treatment options are limited. Isolated hepatic perfusion (IHP) is a locoregional therapy with high response rates but with unclear effect on overall survival (OS).

METHODS

In this phase III randomized controlled multicenter trial (the SCANDIUM trial) patients with previously untreated isolated uveal melanoma liver metastases were included between 2013-2021, with at least 24 months of follow-up. The planned accrual was 90 patients randomized 1:1 to receive a one-time treatment with IHP or BAC. Crossover to IHP was not allowed. The primary endpoint was the 24-month OS rate, with the hypothesis of a treatment effect leading to a 50% OS rate in the IHP group compared to 20% in the control group. HRQOL was measured by the EuroQol 5-domains 3-levels (EQ-5D-3L) questionnaire over 12 months.

RESULTS

The intention-to-treat (ITT) population included 87 patients randomized to the IHP group (43 patients; 41 [89%] received IHP) or the control group (44 patients). The control group received chemotherapy (49%), immunotherapy (39%), or localized interventions (9%). In the ITT population, the median PFS was 7.4 months in the IHP group compared with 3.3 months in the control group, with a hazard ratio of 0.21 (95% CI, 0.12-0.36). The 24-month OS rate was 46.5% in the IHP group versus 29.5% in the control group (P=0.12). The median OS was 21.7 months versus 17.6 months, with a hazard ratio of 0.64 (95% CI, 0.37-1.10). EQ-5D-3L showed a sustained high health status for the IHP group over 12 months, compared to a deteriorating trend in the control group.

CONCLUSIONS

For patients with liver metastases from uveal melanoma, IHP offers high response rates translating to a benefit in PFS including a trend of better HRQOL compared to the control group. However, the primary endpoint of OS at 24 months was not met.

摘要

目的

探讨与最佳替代治疗（BAC）相比，一线孤立性肝灌注（IHP）治疗葡萄膜黑色素瘤肝转移患者的总生存期（OS）和健康相关生活质量（HRQOL）。

总结背景数据

约一半的葡萄膜黑色素瘤患者会发生转移性疾病，最常见于肝脏，且全身治疗选择有限。孤立性肝灌注（IHP）是一种局部区域治疗方法，缓解率高，但对总生存期（OS）的影响尚不清楚。

方法

在这项III期随机对照多中心试验（钪试验）中，纳入了2013年至2021年间未经治疗的孤立性葡萄膜黑色素瘤肝转移患者，随访至少24个月。计划纳入90例患者，按1:1随机分组，接受IHP或BAC的一次性治疗。不允许交叉接受IHP治疗。主要终点是24个月总生存率，假设治疗效果使IHP组的总生存率达到50%，而对照组为20%。通过欧洲五维健康量表（EQ-5D-3L）问卷在12个月内测量HRQOL。

结果

意向性分析（ITT）人群包括87例随机分为IHP组（43例患者；41例[89%]接受IHP治疗）或对照组（44例患者）的患者。对照组接受化疗（49%）、免疫治疗（39%）或局部干预（9%）。在ITT人群中，IHP组的中位无进展生存期（PFS）为7.4个月，而对照组为3.3个月，风险比为0.21（95%CI，0.12-0.36）。IHP组的24个月总生存率为46.5%，对照组为29.5%（P=0.12）。中位总生存期分别为21.7个月和17.6个月，风险比为0.64（95%CI，0.37-1.10）。EQ-5D-3L显示，IHP组在12个月内保持较高的健康状态，而对照组呈恶化趋势。