Systemic Treatment of Metastatic Conjunctival Melanoma

Torres, Simão Pinto; André, Teresa; Gouveia, Emanuel; Costa, L.; Passos, Maria José

doi:10.1155/2017/4623964

Cited by 29 publications

(37 citation statements)

References 19 publications

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“…There is no current clear guideline for the use of targeted therapeutics in metastatic CoM. There are limited anecdotal reports of potential inhibitory success on CoM cell lines and patients with Vemurafenib ± DaBRAFenib ( BRAF V600E inhibitors), MEK , AKT , or PD‐1 immune checkpoint inhibitors (Cao et al, ; Ford et al, ; Maleka, Astrom, Bystrom, & Ullenhag, ; Pinto Torres, Andre, Gouveia, Costa, & Passos, ; Riechardt et al, ; Sagiv et al, ). Notably, one of two patients with BRAF‐ mt CoM treated with a BRAF inhibitor in our institution responded well to treatment (unpublished).…”

Section: Discussionmentioning

confidence: 99%

Conjunctival melanoma copy number alterations and correlation with mutation status, tumor features, and clinical outcome

Kenawy

Kalirai

Sacco

et al. 2019

Pigment Cell Melanoma Res

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Relatively little is known about the genetic aberrations of conjunctival melanomas (CoM) and their correlation with clinical and histomorphological features as well as prognosis. The aim of this large collaborative multicenter study was to determine potential key biomarkers for metastatic risk and any druggable targets for high metastatic risk CoM. Using Affymetrix single nucleotide polymorphism genotyping arrays on 59 CoM, we detected frequent amplifications on chromosome (chr) 6p and deletions on 7q, and characterized mutation‐specific copy number alterations. Deletions on chr 10q11.21‐26.2, a region harboring the tumor suppressor genes, PDCD4, SUFU, NEURL1, PTEN, RASSF4, DMBT1, and C10orf90 and C10orf99, significantly correlated with metastasis (Fisher's exact, p ≤ 0.04), lymphatic invasion (Fisher's exact, p ≤ 0.02), increasing tumor thickness (Mann–Whitney, p ≤ 0.02), and BRAF mutation (Fisher's exact, p ≤ 0.05). This enhanced insight into CoM biology is a step toward identifying patients at risk of metastasis and potential therapeutic targets for systemic disease.

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Section: Discussionmentioning

confidence: 99%

Conjunctival melanoma copy number alterations and correlation with mutation status, tumor features, and clinical outcome

Kenawy

Kalirai

Sacco

et al. 2019

Pigment Cell Melanoma Res

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“…Patients with BRAF -mutated metastatic conjunctival melanoma have shown objective responses to BRAF inhibition in several reported cases but not in all [ 81 , 82 , 83 , 84 ]. BRAF/MEK inhibition showed the stable disease in one metastatic patient and (near) complete responses in two patients with local recurrent disease [ 85 , 86 , 87 ].…”

Section: Genetic Biomarkers When Metastatic Disease Is Presentmentioning

confidence: 99%

Genetic Biomarkers in Melanoma of the Ocular Region: What the Medical Oncologist Should Know

Bol

Donia

Heegaard

et al. 2020

IJMS

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Melanoma of the ocular region (ocular melanoma) comprises about 5% of all patients with melanoma and covers posterior uveal melanoma, iris melanoma, and conjunctival melanoma. The risk of metastasis is much higher in patients with ocular melanoma compared to a primary melanoma of the skin. The subtypes of ocular melanoma have distinct genetic features, which should be taken into consideration when making clinical decisions. Most relevant for current practice is the absence of BRAF mutations in posterior uveal melanoma, although present in some iris melanomas and conjunctival melanomas. In this review, we discuss the genetic biomarkers of the subtypes of ocular melanoma and their impacts on the clinical care of these patients.

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“…One undetermined BRAF V600 mutation has also been reported (0.6%). 34 Other BRAF mutations, such as G469A and D594G are found in 1.2% (n=2) of the mutant BRAF conjunctival melanomas ( Table 1 ). The V600E, V600K, V600R, D594G and G469A single point mutations lead to constitutive activation of the kinase domain of the BRAF protein, and thus, to downstream activation of the MAPK pathway without the need for phosphorylation by RAS.…”

Section: Resultsmentioning

confidence: 99%

“…To date, a total of nine conjunctival melanoma cases have been managed with BRAF and BRAF/MEK inhibitors ( Table 2 ) 28 , 31 , 32 , 34 , 35 , 38 , 40 , 94 Four cases were treated solely with BRAF inhibitor monotherapy, 28 , 32 , 34 , 94 either with vemurafenib 32 , 34 , 94 or dabrafenib. 94 The remaining five cases received BRAF/MEK inhibitor combination therapy 31 , 35 , 38 , 40 with dabrafenib/trametinib 31 , 35 , 38 , 40 and vemurafenib/cobimetinib.…”

Section: Resultsmentioning

confidence: 99%

“… 28 , 32 , 34 , 38 , 40 , 94 Out of the 4 cases that received BRAF inhibitor monotherapy, one patient demonstrated mixed results, with initial improvement followed by disease progression, 28 two patients responded partially to the treatment, 32 , 94 and one patient with metastatic disease was on complete remission at 52 weeks of follow-up. 34 Out of the 3 cases that received BRAF/MEK inhibitor combination therapy alone, 35 , 38 , 40 one patient with metastatic disease demonstrated complete disease remission, 38 while another one showed only partial improvement. 40 The third patient, who had presented with locally advanced conjunctival melanoma, responded substantially to BRAF/MEK inhibition as neoadjuvant therapy, which allowed for the subsequent resection of the shrunk lesion.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

<p>Conjunctival Melanoma: Update on Genetics, Epigenetics and Targeted Molecular and Immune-Based Therapies</p>

Gkiala¹,

Palioura²

2020

OPTH

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Purpose: To present the molecular mechanisms involved in the pathogenesis of conjunctival melanoma (CM) and review the existing literature on targeted molecular inhibitors as well as immune checkpoint inhibitors for the management of locally advanced and metastatic disease. Methods: A comprehensive review of the literature was performed using the keywords "conjunctival melanoma", "immune checkpoint inhibitors", "BRAF inhibitors", "MEK inhibitors", "CTLA4 inhibitors", "PD1 inhibitors", "c-KIT mutations", "BRAF mutations", "NRAS mutations", "dabrafenib", "trametinib", "vemurafenib", "ipilimumab", "pembrolizumab", and "nivolumab". A total of 250 articles were reviewed and 120 were included in this report. Results: Mutations of mediators in the MAP kinase pathway, such as RAS, BRAF, MEK and ERK, and mutations of the PI3K/AKT/mTOR pathway play a major role in the pathogenesis of conjunctival melanoma. In addition, alterations of c-KIT, NF1, TERT, chemokine receptors as well as chromosomal copy number alterations and micro RNAs are thought to have a causative association with CM development. Targeted molecular inhibitors, such as BRAF and MEK inhibitors, are currently being implemented in the therapy of BRAF-mutated CM. Furthermore, immune checkpoint PD-1 and CTLA4 inhibitors with favorable clinical outcomes in the treatment of cutaneous melanoma have increased recurrence-free survival and reduced metastatic spread in CM cases. Conclusion: The complex molecular mechanisms that contribute to the development of CM can be targeted both by molecular inhibitors of oncogenic pathways as well as immune checkpoint inhibitors in order to halt progression of the disease and increase survival.

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Systemic Treatment of Metastatic Conjunctival Melanoma

Cited by 29 publications

References 19 publications

Conjunctival melanoma copy number alterations and correlation with mutation status, tumor features, and clinical outcome

Conjunctival melanoma copy number alterations and correlation with mutation status, tumor features, and clinical outcome

Genetic Biomarkers in Melanoma of the Ocular Region: What the Medical Oncologist Should Know

<p>Conjunctival Melanoma: Update on Genetics, Epigenetics and Targeted Molecular and Immune-Based Therapies</p>

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