Locoregional Therapies for the Treatment of Uveal Melanoma Hepatic Metastases

Gonsalves, Carin F.; Adamo, Robert D.; Eschelman, David J.

doi:10.1055/s-0040-1720948

Cited by 15 publications

(18 citation statements)

References 56 publications

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“…As the liver is the dominant predilection site for UM metastases and survival correlates with disease control in the liver, a variety of liver-directed therapies have been studied. While published literature varies considerably in terms of patient selection, disease extent, design, and outcome measurements, it suggests that locoregional liver therapies offer survival benefit in selected patients with hepatic metastases [ 33 – 36 ].…”

Section: Discussionmentioning

confidence: 99%

Combining Hepatic Percutaneous Perfusion with Ipilimumab plus Nivolumab in advanced uveal melanoma (CHOPIN): study protocol for a phase Ib/randomized phase II trial

Tong

Kooij

Speetjens

et al. 2022

Trials

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Background While immune checkpoint inhibition (ICI) has revolutionized the treatment of metastatic cutaneous melanoma, no standard treatments are available for patients with metastatic uveal melanoma (UM). Several locoregional therapies are effective in the treatment of liver metastases, such as percutaneous hepatic perfusion with melphalan (M-PHP). The available literature suggests that treatment with ICI following locoregional treatment of liver UM metastases can result in clinical response. We hypothesize that combining M-PHP with ICI will lead to enhanced antigen presentation and increased immunomodulatory effect, improving control of both hepatic and extrahepatic disease. Methods Open-label, single-center, phase Ib/randomized phase II trial, evaluating the safety and efficacy of the combination of M-PHP with ipilimumab (anti-CTLA-4 antibody) and nivolumab (anti-PD-1 antibody) in patients with unresectable hepatic metastases of UM in first-line treatment, with or without the limited extrahepatic disease. The primary objective is to determine the safety, toxicity, and efficacy of the combination regimen, defined by maximum tolerated dose (MTD) and progression-free survival (PFS) at 1 year. Secondary objectives include overall survival (OS) and overall response rate (ORR). A maximum of 88 patients will be treated in phase I and phase II combined. Baseline characteristics will be described with descriptive statistics (t-test, chi-square test). To study the association between risk factors and toxicity, a logistic regression model will be applied. PFS and OS will be summarized using Kaplan-Meier curves. Discussion This is the first trial to evaluate this treatment combination by establishing the maximum tolerated dose and evaluating the efficacy of the combination treatment. M-PHP has shown to be a safe and effective treatment for UM patients with liver metastases and became the standard treatment option in our center. The combination of ICI with M-PHP is investigated in the currently described trial which might lead to a better treatment response both in and outside the liver. Trial Registration This trial was registered in the US National Library of Medicine with identifier NCT04283890. Registered as per February 2020 - Retrospectively registered. EudraCT registration number: 2018-004248-49. Local MREC registration number: NL60508.058.19.

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Section: Discussionmentioning

confidence: 99%

Combining Hepatic Percutaneous Perfusion with Ipilimumab plus Nivolumab in advanced uveal melanoma (CHOPIN): study protocol for a phase Ib/randomized phase II trial

Tong

Kooij

Speetjens

et al. 2022

Trials

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“…The hepatotropism of UM contributes to the development of liver-directed therapy methods [105][106][107][108][109][110][111][112][113][114][115][116][117][118][119][120][121][122][123] (Table 2, Ref. [28,95,[108][109][110]112,113,115,[118][119][120][121][122][123]). In certain cases, surgical removal of metastatic nodules can offer long-term survival benefit.…”

Section: Liver-directed Therapiesmentioning

confidence: 99%

“…• Option for patients with liver predominant disease • Significantly longer PFS compared to intravenous administration of chemotherapy [112,113,118] • High concentrations of chemotherapeutic agent in the liver • OS ranging from 10 to 24 months…”

Section: Hepatic Arterial Infusion Of Chemotherapymentioning

confidence: 99%

Liver metastasis in uveal melanoma — treatment options and clinical outcome

Kaštelan¹,

Zimak²,

Ivanković³

et al. 2022

Front. Biosci. (Landmark Ed)

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Uveal melanoma (UM) is the most prevalent primary intraocular malignancy in adults with a stable incidence rate between five and seven cases per million in Europe and the United States. Although UM and melanoma from other sites have the same origin, UM has different epidemiological, biological, pathological and clinical features including characteristic metastatic hepatotropism. Despite improvements in the treatment of primary tumours, approximately 50% of patients with UM will develop metastases. In 90% of cases the liver is the first site of metastasis, however the mechanisms underlying this hepatic tropism have not been elucidated. Metastatic disease is associated with a very poor prognosis with a median overall survival of 6 to 12 months. Currently, there is no standard systemic treatment available for metastatic UM and once liver metastases have developed, prognosis is relatively poor. In order to prolong survival, close follow-up in all patients with UM is recommended for early detection and treatment. The treatment of metastatic UM includes systemic chemotherapy, immunotherapy and molecular targeted therapy. Liver-directed therapies, such as resection, radioembolization, chemoembolization, immunoembolization, isolated and percutaneous liver perfusion as well as thermal ablation represent available treatment options. However, to date a consensus regarding the optimal method of treatment is still lacking and the importance of setting guidelines in the treatment and management of metastatic UM is becoming a priority. Improvement in knowledge and a better insight into tumour biology, immunology and metastatic mechanism may improve current treatment methods and lead to the development of new strategies paving the way for a personalized approach.

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“…Up to 50% of patients will develop metastatic disease with the liver being the primary predilection site [2,3]. Without treatment, metastasized UM has a poor prognosis with reported survival rates of two to nine months after diagnosis [4]. Less than 10% of patients are eligible for resection or thermal ablation, as metastases are often bilobar and diffuse [4,5].…”

Section: Introductionmentioning

confidence: 99%

Predictive Parameters in Patients Undergoing Percutaneous Hepatic Perfusion with Melphalan for Unresectable Liver Metastases from Uveal Melanoma: A Retrospective Pooled Analysis

Tong

Samim

Meijer

et al. 2022

Cardiovasc Intervent Radiol

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Purpose The aim of this study was to identify positive predictors for survival in uveal melanoma (UM) patients treated with percutaneous hepatic perfusion with melphalan (M-PHP), by retrospectively pooling data from three centers. Materials and Methods Retrospective analysis including patients ($$\ge$$ ≥ 18 years) treated with M-PHP between February 2014 and December 2019 for unresectable liver-dominant or liver-only metastases from UM. Predictors for OS were assessed using uni- and multivariate analyses. Other study outcome measures were response rate, progression-free survival (PFS), liver progression-free survival (LPFS), overall survival (OS) and complications according to CTCAEv5.0. Results In total, 101 patients (47.5% males; median age 59.0 years) completed a minimum of one M-PHP. At a median follow-up time of 15.0 months, complete response (CR), partial response (PR), stable disease (SD) and progressive disease were seen in five (5.0%), 55 (54.5%), 30 (29.7%) and 11 (10.9%) patients, respectively, leading to a 89.1% disease control rate. Median PFS, LPFS and OS were 9.0, 11.0 and 20.0 months, respectively. Survival analyses stratified for radiological response demonstrated significant improved survival in patients with CR or PR and SD category. Treatment of the primary tumor with radiotherapy, ≥ 2 M-PHP and lactate dehydrogenase (LDH) < 248 U/L were correlated with improved OS. Thirty-day mortality was 1.1% (n = 2). Most common complication was hematological toxicity (self-limiting in most cases). Conclusion M-PHP is safe and effective in patients with UM liver metastases. Achieving CR, PR or SD is associated with improved survival. Primary tumor treatment with radiotherapy, normal baseline LDH and > 1 M-PHP cycles are associated with improved OS.

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Locoregional Therapies for the Treatment of Uveal Melanoma Hepatic Metastases

Cited by 15 publications

References 56 publications

Combining Hepatic Percutaneous Perfusion with Ipilimumab plus Nivolumab in advanced uveal melanoma (CHOPIN): study protocol for a phase Ib/randomized phase II trial

Combining Hepatic Percutaneous Perfusion with Ipilimumab plus Nivolumab in advanced uveal melanoma (CHOPIN): study protocol for a phase Ib/randomized phase II trial

Liver metastasis in uveal melanoma — treatment options and clinical outcome

Predictive Parameters in Patients Undergoing Percutaneous Hepatic Perfusion with Melphalan for Unresectable Liver Metastases from Uveal Melanoma: A Retrospective Pooled Analysis

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