Jonathan S Zager, Marlana Orloff, Pier Francesco Ferrucci, Junsung Choi, David J Eschelman, Evan S Glazer, Aslam Ejaz, J Harrison Howard, Erika Richtig, Sebastian Ochsenreither, Sunil A Reddy, Michael C Lowe, Georgia M Beasley, Anja Gesierich, Armin Bender, Martin Gschnell, Reinhard Dummer, Michel Rivoire, Ana Arance, Stephen William Fenwick, Joseph J Sacco, Sebastian Haferkamp, Carsten Weishaupt, Johnny John, Matthew Wheater, Christian H Ottensmeier
{"title":"一项开放标签,随机研究Melphalan/肝给药系统与最佳替代治疗在不可切除转移性葡萄膜黑色素瘤患者中的应用。","authors":"Jonathan S Zager, Marlana Orloff, Pier Francesco Ferrucci, Junsung Choi, David J Eschelman, Evan S Glazer, Aslam Ejaz, J Harrison Howard, Erika Richtig, Sebastian Ochsenreither, Sunil A Reddy, Michael C Lowe, Georgia M Beasley, Anja Gesierich, Armin Bender, Martin Gschnell, Reinhard Dummer, Michel Rivoire, Ana Arance, Stephen William Fenwick, Joseph J Sacco, Sebastian Haferkamp, Carsten Weishaupt, Johnny John, Matthew Wheater, Christian H Ottensmeier","doi":"10.1245/s10434-025-17231-x","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Metastatic uveal melanoma (mUM) has a poor prognosis, with liver metastases typically presenting a therapeutic challenge. Melphalan/Hepatic Delivery System (Melphalan/HDS) is a drug/medical device combination used for liver-directed treatment of unresectable mUM patients. This study assessed efficacy and safety of Melphalan/HDS versus best alternative care (BAC).</p><p><strong>Methods: </strong>Eligible patients with unresectable mUM were randomized (1:1) to receive Melphalan/HDS (3 mg/kg ideal body weight) once every 6 to 8 weeks for a maximum of 6 cycles or BAC. Due to slow enrollment and patient reluctance to receive BAC treatment, the study design was amended to a single-arm Melphalan/HDS study, and all efficacy analyses of the randomized study were treated as exploratory.</p><p><strong>Results: </strong>The study enrolled 85 patients. Eligible patients were randomized to receive Melphalan/HDS (n = 43) or BAC (n = 42), and 72 patients received study treatment (Melphalan/HDS [n = 40]; BAC [n = 32]). Exploratory analyses of efficacy endpoints showed numerical differences consistently favoring the Melphalan/HDS arm versus BAC (median overall survival: 18.5 vs. 14.5 months; median progression-free survival: 9.1 vs. 3.3 months; objective response rate: 27.5% vs. 9.4%; and disease control rate: 80.0% vs. 46.9%). Serious adverse events (SAEs) occurred in 51.2% of Melphalan/HDS and in 21.9% of BAC patients. The most common (>5%) SAEs included thrombocytopenia (19.5%), neutropenia (9.8%), leukopenia (9.8%) and febrile neutropenia (7.3%) in Melphalan/HDS patients and cholecystitis, nausea and vomiting (6.3% each) in BAC patients. No treatment-related deaths were observed.</p><p><strong>Conclusion: </strong>Treatment with Melphalan/HDS shows clinically meaningful efficacy and demonstrates a favorable benefit-risk profile in patients with unresectable mUM as compared to BAC.</p>","PeriodicalId":8229,"journal":{"name":"Annals of Surgical Oncology","volume":" ","pages":""},"PeriodicalIF":3.4000,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"An Open-label, Randomized Study of Melphalan/Hepatic Delivery System Versus Best Alternative Care in Patients with Unresectable Metastatic Uveal Melanoma.\",\"authors\":\"Jonathan S Zager, Marlana Orloff, Pier Francesco Ferrucci, Junsung Choi, David J Eschelman, Evan S Glazer, Aslam Ejaz, J Harrison Howard, Erika Richtig, Sebastian Ochsenreither, Sunil A Reddy, Michael C Lowe, Georgia M Beasley, Anja Gesierich, Armin Bender, Martin Gschnell, Reinhard Dummer, Michel Rivoire, Ana Arance, Stephen William Fenwick, Joseph J Sacco, Sebastian Haferkamp, Carsten Weishaupt, Johnny John, Matthew Wheater, Christian H Ottensmeier\",\"doi\":\"10.1245/s10434-025-17231-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Metastatic uveal melanoma (mUM) has a poor prognosis, with liver metastases typically presenting a therapeutic challenge. Melphalan/Hepatic Delivery System (Melphalan/HDS) is a drug/medical device combination used for liver-directed treatment of unresectable mUM patients. This study assessed efficacy and safety of Melphalan/HDS versus best alternative care (BAC).</p><p><strong>Methods: </strong>Eligible patients with unresectable mUM were randomized (1:1) to receive Melphalan/HDS (3 mg/kg ideal body weight) once every 6 to 8 weeks for a maximum of 6 cycles or BAC. Due to slow enrollment and patient reluctance to receive BAC treatment, the study design was amended to a single-arm Melphalan/HDS study, and all efficacy analyses of the randomized study were treated as exploratory.</p><p><strong>Results: </strong>The study enrolled 85 patients. Eligible patients were randomized to receive Melphalan/HDS (n = 43) or BAC (n = 42), and 72 patients received study treatment (Melphalan/HDS [n = 40]; BAC [n = 32]). Exploratory analyses of efficacy endpoints showed numerical differences consistently favoring the Melphalan/HDS arm versus BAC (median overall survival: 18.5 vs. 14.5 months; median progression-free survival: 9.1 vs. 3.3 months; objective response rate: 27.5% vs. 9.4%; and disease control rate: 80.0% vs. 46.9%). Serious adverse events (SAEs) occurred in 51.2% of Melphalan/HDS and in 21.9% of BAC patients. The most common (>5%) SAEs included thrombocytopenia (19.5%), neutropenia (9.8%), leukopenia (9.8%) and febrile neutropenia (7.3%) in Melphalan/HDS patients and cholecystitis, nausea and vomiting (6.3% each) in BAC patients. No treatment-related deaths were observed.</p><p><strong>Conclusion: </strong>Treatment with Melphalan/HDS shows clinically meaningful efficacy and demonstrates a favorable benefit-risk profile in patients with unresectable mUM as compared to BAC.</p>\",\"PeriodicalId\":8229,\"journal\":{\"name\":\"Annals of Surgical Oncology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2025-04-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annals of Surgical Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1245/s10434-025-17231-x\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Surgical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1245/s10434-025-17231-x","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景:转移性葡萄膜黑色素瘤(mUM)预后较差,肝转移通常是治疗难题。美法仑/肝脏给药系统(Melphalan/HDS)是一种药物/医疗设备组合,用于对无法切除的黑色素瘤患者进行肝脏定向治疗。本研究评估了美法仑/HDS与最佳替代治疗(BAC)的疗效和安全性:对符合条件的不可切除的MUM患者进行随机分组(1:1),接受美法仑/HDS(3毫克/千克理想体重)治疗,每6至8周一次,最多6个周期;或接受BAC治疗。由于入组缓慢以及患者不愿接受BAC治疗,研究设计被修改为单臂美法仑/HDS研究,随机研究的所有疗效分析均被视为探索性分析:研究共招募了 85 名患者。符合条件的患者被随机分配接受美法仑/HDS(n = 43)或BAC(n = 42)治疗,72名患者接受了研究治疗(美法仑/HDS [n = 40]; BAC [n = 32])。疗效终点的探索性分析表明,美法仑/HDS治疗组与BAC治疗组相比,在数字上始终存在差异(中位总生存期:18.5个月 vs. 14.5个月;中位无进展生存期:9.1个月 vs. 3.3个月;客观反应率:27.5% vs. 9.4%;疾病控制率:80.0% vs. 46.0%):80.0%对46.9%)。51.2%的美法仑/HDS患者和21.9%的BAC患者发生了严重不良事件(SAE)。最常见(>5%)的SAE包括美法仑/HDS患者的血小板减少症(19.5%)、中性粒细胞减少症(9.8%)、白细胞减少症(9.8%)和发热性中性粒细胞减少症(7.3%),以及BAC患者的胆囊炎、恶心和呕吐(各占6.3%)。没有观察到与治疗相关的死亡病例:结论:与 BAC 相比,美法仑/HDS 对不可切除的 MUM 患者具有临床意义上的疗效,并显示出良好的获益风险特征。
An Open-label, Randomized Study of Melphalan/Hepatic Delivery System Versus Best Alternative Care in Patients with Unresectable Metastatic Uveal Melanoma.
Background: Metastatic uveal melanoma (mUM) has a poor prognosis, with liver metastases typically presenting a therapeutic challenge. Melphalan/Hepatic Delivery System (Melphalan/HDS) is a drug/medical device combination used for liver-directed treatment of unresectable mUM patients. This study assessed efficacy and safety of Melphalan/HDS versus best alternative care (BAC).
Methods: Eligible patients with unresectable mUM were randomized (1:1) to receive Melphalan/HDS (3 mg/kg ideal body weight) once every 6 to 8 weeks for a maximum of 6 cycles or BAC. Due to slow enrollment and patient reluctance to receive BAC treatment, the study design was amended to a single-arm Melphalan/HDS study, and all efficacy analyses of the randomized study were treated as exploratory.
Results: The study enrolled 85 patients. Eligible patients were randomized to receive Melphalan/HDS (n = 43) or BAC (n = 42), and 72 patients received study treatment (Melphalan/HDS [n = 40]; BAC [n = 32]). Exploratory analyses of efficacy endpoints showed numerical differences consistently favoring the Melphalan/HDS arm versus BAC (median overall survival: 18.5 vs. 14.5 months; median progression-free survival: 9.1 vs. 3.3 months; objective response rate: 27.5% vs. 9.4%; and disease control rate: 80.0% vs. 46.9%). Serious adverse events (SAEs) occurred in 51.2% of Melphalan/HDS and in 21.9% of BAC patients. The most common (>5%) SAEs included thrombocytopenia (19.5%), neutropenia (9.8%), leukopenia (9.8%) and febrile neutropenia (7.3%) in Melphalan/HDS patients and cholecystitis, nausea and vomiting (6.3% each) in BAC patients. No treatment-related deaths were observed.
Conclusion: Treatment with Melphalan/HDS shows clinically meaningful efficacy and demonstrates a favorable benefit-risk profile in patients with unresectable mUM as compared to BAC.
期刊介绍:
The Annals of Surgical Oncology is the official journal of The Society of Surgical Oncology and is published for the Society by Springer. The Annals publishes original and educational manuscripts about oncology for surgeons from all specialities in academic and community settings.