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04-05-2024 | Choroidal Melanoma | Hepatobiliary Tumors

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

Authors: Jonathan S. Zager, MD, FACS, Marlana Orloff, MD, Pier Francesco Ferrucci, MD, Junsung Choi, MD, David J. Eschelman, MD, FSIR, Evan S. Glazer, MD, PhD, FACS, Aslam Ejaz, MD, J. Harrison Howard, MD, Erika Richtig, MD, Sebastian Ochsenreither, MD, Sunil A. Reddy, MD, Michael C. Lowe, MD, Georgia M. Beasley, MD, Anja Gesierich, MD, Armin Bender, MD, Martin Gschnell, MD, Reinhard Dummer, MD, Michel Rivoire, MD, Ana Arance, MD, PhD, Stephen William Fenwick, MD, FRCS, Joseph J. Sacco, MD, Sebastian Haferkamp, MD, Carsten Weishaupt, MD, Johnny John, MD, Matthew Wheater, MD, PhD, MRCP, Christian H. Ottensmeier, MD, PhD, FRCP

Published in: Annals of Surgical Oncology

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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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Metadata
Title
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
Authors
Jonathan S. Zager, MD, FACS
Marlana Orloff, MD
Pier Francesco Ferrucci, MD
Junsung Choi, MD
David J. Eschelman, MD, FSIR
Evan S. Glazer, MD, PhD, FACS
Aslam Ejaz, MD
J. Harrison Howard, MD
Erika Richtig, MD
Sebastian Ochsenreither, MD
Sunil A. Reddy, MD
Michael C. Lowe, MD
Georgia M. Beasley, MD
Anja Gesierich, MD
Armin Bender, MD
Martin Gschnell, MD
Reinhard Dummer, MD
Michel Rivoire, MD
Ana Arance, MD, PhD
Stephen William Fenwick, MD, FRCS
Joseph J. Sacco, MD
Sebastian Haferkamp, MD
Carsten Weishaupt, MD
Johnny John, MD
Matthew Wheater, MD, PhD, MRCP
Christian H. Ottensmeier, MD, PhD, FRCP
Publication date
04-05-2024
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-024-15293-x
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