Efficacy and Safety of the Melphalan/Hepatic Delivery System in Patients with Unresectable Metastatic Uveal Melanoma: Results from an Open-Label, Single-Arm, Multicenter Phase 3 Study
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| Titel: | Efficacy and Safety of the Melphalan/Hepatic Delivery System in Patients with Unresectable Metastatic Uveal Melanoma: Results from an Open-Label, Single-Arm, Multicenter Phase 3 Study |
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| Autoren: | 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 |
| Quelle: | Ann Surg Oncol |
| Verlagsinformationen: | Springer Science and Business Media LLC, 2024. |
| Publikationsjahr: | 2024 |
| Schlagwörter: | Male, Uveal Neoplasms, Adult, Aged, 80 and over, Liver Neoplasms, Middle Aged, Prognosis, Female [MeSH], Follow-Up Studies [MeSH], Aged, 80 and over [MeSH], Aged [MeSH], Adult [MeSH], Humans [MeSH], Drug Delivery Systems [MeSH], Melanoma/secondary [MeSH], Uveal Neoplasms/drug therapy [MeSH], Melphalan/administration, Antineoplastic Agents, Alkylating/therapeutic use [MeSH], Middle Aged [MeSH], Melanoma/mortality [MeSH], Survival Rate [MeSH], Male [MeSH], Liver Neoplasms/secondary [MeSH], Melanoma/pathology [MeSH], Prognosis [MeSH], Antineoplastic Agents, Alkylating/administration, Hepatobiliary Tumors, Uveal Neoplasms/pathology [MeSH], Melanoma/drug therapy [MeSH], Liver Neoplasms/drug therapy [MeSH], Uveal Neoplasms/mortality [MeSH], Survival Rate, 03 medical and health sciences, Drug Delivery Systems, 0302 clinical medicine, Uveal Melanoma, Humans, Female, Melanoma, Melphalan, Antineoplastic Agents, Alkylating, Aged, Follow-Up Studies |
| Beschreibung: | Background Uveal melanoma (UM) has a poor prognosis once liver metastases occur. The melphalan/Hepatic Delivery System (melphalan/HDS) is a drug/device combination used for liver-directed treatment of metastatic UM (mUM) patients. The purpose of the FOCUS study was to assess the efficacy and safety of melphalan/HDS in patients with unresectable mUM. Methods Eligible patients with mUM received treatment with melphalan (3.0 mg/kg ideal body weight) once every 6 to 8 weeks for a maximum of six cycles. The primary end point was the objective response rate (ORR). The secondary end points included duration of response (DOR), overall survival (OS), and progression-free survival (PFS). Results The study enrolled 102 patients with mUM. Treatment was attempted in 95 patients, and 91 patients received treatment. In the treated population (n = 91), the ORR was 36.3 % (95 % confidence interval [CI], 26.44–47.01), including 7.7 % of patients with a complete response. Thus, the study met its primary end point because the lower bound of the 95 % CI for ORR exceeded the upper bound (8.3 %) from the benchmark meta-analysis. The median DOR was 14 months, and the median OS was 20.5 months, with an OS of 80 % at 1 year. The median PFS was 9 months, with a PFS of 65 % at 6 months. The most common serious treatment-emergent adverse events were thrombocytopenia (15.8 %) and neutropenia (10.5 %), treated mostly on an outpatient basis with observation. No treatment-related deaths were observed. Conclusion Treatment with melphalan/HDS provides a clinically meaningful response rate and demonstrates a favorable benefit-risk profile in patients with unresectable mUM (study funded by Delcath; ClinicalTrials.gov identifier: NCT02678572; EudraCT no. 2015-000417-44). |
| Publikationsart: | Article Other literature type |
| Sprache: | English |
| ISSN: | 1534-4681 1068-9265 |
| DOI: | 10.1245/s10434-024-15293-x |
| Zugangs-URL: | https://pubmed.ncbi.nlm.nih.gov/38704501 https://repository.publisso.de/resource/frl:6504059 |
| Rights: | CC BY |
| Dokumentencode: | edsair.doi.dedup.....bece7342460c1de7627fdbcc8b5c47c0 |
| Datenbank: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstract: | Background Uveal melanoma (UM) has a poor prognosis once liver metastases occur. The melphalan/Hepatic Delivery System (melphalan/HDS) is a drug/device combination used for liver-directed treatment of metastatic UM (mUM) patients. The purpose of the FOCUS study was to assess the efficacy and safety of melphalan/HDS in patients with unresectable mUM. Methods Eligible patients with mUM received treatment with melphalan (3.0 mg/kg ideal body weight) once every 6 to 8 weeks for a maximum of six cycles. The primary end point was the objective response rate (ORR). The secondary end points included duration of response (DOR), overall survival (OS), and progression-free survival (PFS). Results The study enrolled 102 patients with mUM. Treatment was attempted in 95 patients, and 91 patients received treatment. In the treated population (n = 91), the ORR was 36.3 % (95 % confidence interval [CI], 26.44–47.01), including 7.7 % of patients with a complete response. Thus, the study met its primary end point because the lower bound of the 95 % CI for ORR exceeded the upper bound (8.3 %) from the benchmark meta-analysis. The median DOR was 14 months, and the median OS was 20.5 months, with an OS of 80 % at 1 year. The median PFS was 9 months, with a PFS of 65 % at 6 months. The most common serious treatment-emergent adverse events were thrombocytopenia (15.8 %) and neutropenia (10.5 %), treated mostly on an outpatient basis with observation. No treatment-related deaths were observed. Conclusion Treatment with melphalan/HDS provides a clinically meaningful response rate and demonstrates a favorable benefit-risk profile in patients with unresectable mUM (study funded by Delcath; ClinicalTrials.gov identifier: NCT02678572; EudraCT no. 2015-000417-44). |
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| ISSN: | 15344681 10689265 |
| DOI: | 10.1245/s10434-024-15293-x |