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.
J Clin Oncol. 2023 Jun 1;41(16):3042-3050. doi: 10.1200/JCO.22.01705. Epub 2023 Mar 20.
About half of patients with metastatic uveal melanoma present with isolated liver metastasis, in whom the median survival is 6-12 months. The few systemic treatment options available only moderately prolong survival. Isolated hepatic perfusion (IHP) with melphalan is a regional treatment option, but prospective efficacy and safety data are lacking.
In this multicenter, randomized, open-label, phase III trial, patients with previously untreated isolated liver metastases from uveal melanoma were randomly assigned to receive a one-time treatment with IHP with melphalan or best alternative care (control group). The primary end point was overall survival at 24 months. Here, we report the secondary outcomes of response according to RECIST 1.1 criteria, progression-free survival (PFS), hepatic PFS (hPFS), and safety.
Ninety-three patients were randomly assigned, and 87 patients were assigned to either IHP (n = 43) or a control group receiving the investigator's choice of treatment (n = 44). In the control group, 49% received chemotherapy, 39% immune checkpoint inhibitors, and 9% locoregional treatment other than IHP. In an intention-to-treat analysis, the overall response rates (ORRs) were 40% versus 4.5% in the IHP and control groups, respectively ( < .0001). The median PFS was 7.4 months versus 3.3 months ( < .0001), with a hazard ratio of 0.21 (95% CI, 0.12 to 0.36), and the median hPFS was 9.1 months versus 3.3 months ( < .0001), both favoring the IHP arm. There were 11 treatment-related serious adverse events in the IHP group compared with seven in the control group. There was one treatment-related death in the IHP group.
IHP treatment resulted in superior ORR, hPFS, and PFS compared with best alternative care in previously untreated patients with isolated liver metastases from primary uveal melanoma.
约一半转移性葡萄膜黑素瘤患者表现为孤立性肝转移，其中位生存期为 6-12 个月。现有的少数全身性治疗方案仅能适度延长生存期。甲氨蝶呤孤立性肝灌注（IHP）是一种局部治疗选择，但缺乏前瞻性疗效和安全性数据。
在这项多中心、随机、开放标签、III 期试验中，未经治疗的原发性葡萄膜黑素瘤孤立性肝转移患者被随机分配接受一次 IHP 联合甲氨蝶呤治疗或最佳替代治疗（对照组）。主要终点为 24 个月时的总生存期。此处报告了根据 RECIST 1.1 标准的次要终点反应、无进展生存期（PFS）、肝 PFS（hPFS）和安全性。
93 例患者被随机分配，87 例患者被分配至 IHP 组（n = 43）或接受研究者选择治疗的对照组（n = 44）。在对照组中，49%接受化疗，39%接受免疫检查点抑制剂，9%接受除 IHP 以外的局部区域治疗。在意向治疗分析中，IHP 组和对照组的总缓解率（ORR）分别为 40%和 4.5%（<.0001）。中位 PFS 分别为 7.4 个月和 3.3 个月（<.0001），风险比为 0.21（95%CI，0.12 至 0.36），中位 hPFS 分别为 9.1 个月和 3.3 个月（<.0001），均有利于 IHP 组。IHP 组有 11 例治疗相关严重不良事件，对照组有 7 例。IHP 组有 1 例治疗相关死亡。
与最佳替代治疗相比，IHP 治疗在未经治疗的原发性葡萄膜黑素瘤孤立性肝转移患者中可带来更高的 ORR、hPFS 和 PFS。
