Long-term survival benefit from ipilimumab treatment in metastatic uveal melanoma patients.

Deo, Mugdha

doi:10.1200/jco.2014.32.15_suppl.3060

Cited by 15 publications

(10 citation statements)

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“…In contrast to the 3 European studies from Germany, Italy and Netherlands who all used 3 mg/kg ipilimumab, the median OS was between 9 and 10 months for patients with UM who were treated with ipilimumab in further four retrospective studies [19,21–23]. Besides the study from Deo et al [23] with a reported 1-year OS rate of 46%, none of these retrospective studies reported a 1-year OS rate (S1 Table). Apart from our trial, there is only one further clinical phase II study of the Spanish Melanoma Group (GEM) evaluating the efficacy of 10 mg/kg ipilimumab in 32 patients with treatment-naïve metastatic UM [17].…”

Section: Discussionmentioning

confidence: 98%

“…The 1-year OS rate and the median OS for patients in the Dutch EAP were 27% and 5.2 months, respectively [20] and in the Italian EAP calculated 31% and 6 months, respectively [18]. In contrast to the 3 European studies from Germany, Italy and Netherlands who all used 3 mg/kg ipilimumab, the median OS was between 9 and 10 months for patients with UM who were treated with ipilimumab in further four retrospective studies [19,21–23]. Besides the study from Deo et al [23] with a reported 1-year OS rate of 46%, none of these retrospective studies reported a 1-year OS rate (S1 Table).…”

Section: Discussionmentioning

confidence: 99%

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Phase II DeCOG-Study of Ipilimumab in Pretreated and Treatment-Naïve Patients with Metastatic Uveal Melanoma

Zimmer

Vaübel

Mohr³

et al. 2015

PLoS ONE

214

163

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PurposeUp to 50% of patients with uveal melanoma (UM) develop metastatic disease with limited treatment options. The immunomodulating agent ipilimumab has shown an overall survival (OS) benefit in patients with cutaneous metastatic melanoma in two phase III trials. As patients with UM were excluded in these studies, the Dermatologic Cooperative Oncology Group (DeCOG) conducted a phase II to assess the efficacy and safety of ipilimumab in patients with metastatic UM.Patients and MethodsWe undertook a multicenter phase II study in patients with different subtypes of metastatic melanoma. Here we present data on patients with metastatic UM (pretreated and treatment-naïve) who received up to four cycles of ipilimumab administered at a dose of 3 mg/kg in 3 week intervals. Tumor assessments were conducted at baseline, weeks 12, 24, 36 and 48 according to RECIST 1.1 criteria. Adverse events (AEs), including immune-related AEs were graded according to National Cancer Institute Common Toxicity Criteria (CTC) v.4.0. Primary endpoint was the OS rate at 12 months.ResultsForty five pretreated (85%) and eight treatment-naïve (15%) patients received at least one dose of ipilimumab. 1-year and 2-year OS rates were 22% and 7%, respectively. Median OS was 6.8 months (95% CI 3.7–8.1), median progression-free survival 2.8 months (95% CI 2.5–2.9). The disease control rate at weeks 12 and 24 was 47% and 21%, respectively. Sixteen patients had stable disease (47%), none experienced partial or complete response. Treatment-related AEs were observed in 35 patients (66%), including 19 grade 3–4 events (36%). One drug-related death due to pancytopenia was observed.ConclusionsIpilimumab has very limited clinical activity in patients with metastatic UM. Toxicity was manageable when treated as per protocol-specific guidelines.Trial RegistrationClinicalTrials.gov NCT01355120

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Phase II DeCOG-Study of Ipilimumab in Pretreated and Treatment-Naïve Patients with Metastatic Uveal Melanoma

Zimmer

Vaübel

Mohr³

et al. 2015

PLoS ONE

214

163

View full text Add to dashboard Cite

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“…Although it is beyond the scope of this article to review available clinical data on immune checkpoint therapy trials in metastatic UM, to date, these treatments have shown limited activity. Based on six retrospective studies, ipilimumab, a monoclonal antibody targeting CTLA‐4, has shown response rates ranging from 0% to 5% and median OS ranging from 5.2 to 10.3 months (Danielli et al., ; Deo, ; Kelderman et al., ; Khattak, Fisher, Hughes, Gore, & Larkin, ; Luke et al., ; Maio et al., ). Further, the largest retrospective study using anti‐PD‐1 and anti‐PD‐L1 immunotherapy in 58 patients with metastatic UM showed an objective RR of only 3.6%, median PFS of 2.6 months, and median OS of 7.6 months (Algazi et al., ).…”

Section: Oncogenic Signalingmentioning

confidence: 99%

Oncogenic signaling in uveal melanoma

Park

Diefenbach

Joshua

et al. 2018

Pigment Cell Melanoma Res

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Uveal melanoma is the most common primary cancer of the eye, and despite rapidly emerging insights into the molecular profile of this disease, prognosis of patients with metastatic uveal melanoma remains poor with mortality rates unchanged in over 35 years. Early genetic events activate G protein-coupled receptor signaling in nearly all uveal tumors via mutually exclusive mutations in the GNAQ, GNA11, CYSLTR2, or PLCB4 genes. A multitude of signaling cascades downstream of G protein activation, including protein kinase C and mitogen-activated protein kinase activity, are actionable, and many ongoing clinical trials are targeting these pathways. Additional cytogenetic and genetic changes, however, including chromosome 3 monosomy, mutations in the BAP1 tumor suppressor gene, alterations in the splicing factors SRSF2/SF3B1, and mutations in the translation initiation factor EIF1AX, modulate signaling output in uveal tumors and modify the risk of metastases. Here, we review the complex interactions between genetic, molecular signaling, and prognostic profiles in uveal melanoma; the clinical implications of these interactions; and the latest potential targets for rational therapy.

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“…Response rates of ∼5%–10% have been reported from evaluations in metastatic uveal melanoma,47–50 but evidence of a median overall survival (OS) of 6.0–9.7 months in these trials suggests that responses could be delayed and durable in only a minority of patients 4849 Preliminary data from the phase II GEM-1 trial in treatment-naïve patients suggested more promising response rates than previously reported 51.…”

Section: Metastatic Diseasementioning

confidence: 97%

Metastatic disease from uveal melanoma: treatment options and future prospects

et al. 2016

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Uveal melanoma represents ∼85% of all ocular melanomas and up to 50% of patients develop metastatic disease. Metastases are most frequently localised to the liver and, as few patients are candidates for potentially curative surgery, this is associated with a poor prognosis. There is currently little published evidence for the optimal management and treatment of metastatic uveal melanoma and the lack of effective therapies in this setting has led to the widespread use of systemic treatments for patients with cutaneous melanoma. Uveal and cutaneous melanomas are intrinsically different diseases and so dedicated management strategies and therapies for uveal melanoma are much needed. This review explores the biology of uveal melanoma and how this relates to ongoing trials of targeted therapies in the metastatic disease setting. In addition, we consider the options to optimise patient management and care.

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Long-term survival benefit from ipilimumab treatment in metastatic uveal melanoma patients.

Cited by 15 publications

References 0 publications

Phase II DeCOG-Study of Ipilimumab in Pretreated and Treatment-Naïve Patients with Metastatic Uveal Melanoma

Phase II DeCOG-Study of Ipilimumab in Pretreated and Treatment-Naïve Patients with Metastatic Uveal Melanoma

Oncogenic signaling in uveal melanoma

Metastatic disease from uveal melanoma: treatment options and future prospects

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