Abstract
Uveal melanoma (UM) is the most common intraocular malignancy in adults and shows a high rate of metastatic spread. As randomized clinical trials with immune checkpoint inhibitors (ICI) have not been performed in patients with metastatic UM, we analyzed the real-world outcomes in a nationwide population-based study. Clinical data of patients with UM were extracted from the Danish Metastatic Melanoma database, a nationwide database containing unselected records of patients diagnosed with metastatic melanoma in Denmark. Survival before (pre-ICI, n = 32) and after (post-ICI, n = 94) the approval of first-line treatment with ICI was analyzed. A partial response to first-line treatment was observed in 7% of patients treated with anti-programmed cell death protein (PD)-1 monotherapy and in 21% with combined anti-cytotoxic T lymphocyte antigen (CTLA)-4 plus anti-PD-1 therapy. Median progression-free survival was 2.5 months for patients treated in the pre-ICI era compared to 3.5 months in the post-ICI era (hazard ratio (HR) 0.43; 95% confidence interval (CI) 0.28–0.67; p < 0.001). The estimated one-year overall survival rate increased from 25.0% to 41.9% and the median overall survival improved from 7.8 months to 10.0 months, respectively (HR 0.52; 95% CI 0.34–0.79; p = 0.003). Thus, the introduction of ICI as first-line treatment appears to have significantly improved the real-world survival of patients with metastatic UM, despite relatively low response rates compared to cutaneous melanoma. With the lack of therapies proven effective in randomized trials, these data support the current treatment with ICI in patients with metastatic UM.
Highlights
Uveal melanoma (UM) is the most common intraocular malignancy in adults and it arises in the melanocytes in the uveal tract of the eye, mainly in the choroid
Following drug approvals in cutaneous melanoma (CM) over the past decade, the first-line treatment shifted from chemotherapy to immunotherapy, with the immune checkpoint inhibitors (ICI) such as anti-cytotoxic T lymphocyte antigen (CTLA)-4 or anti-programmed cell death protein (PD)-1 antibodies in multiple countries
As the records were categorized as ocular melanoma in the Danish Metastatic Melanoma database, diagnosis of primary UM was confirmed via the Copenhagen
Summary
Uveal melanoma (UM) is the most common intraocular malignancy in adults and it arises in the melanocytes in the uveal tract of the eye, mainly in the choroid. Cancers 2019, 11, 1489 genes are mutated and where in CM lymphogenic spread is common, it does not occur in UM. With the lack of effective standard-of-care treatment for metastatic UM, most guidelines recommend participation in clinical trials [6,7]. Most patients are treated with the drugs approved for metastatic CM, despite lack of evidence for efficacy in metastatic UM. In contrast to CM, BRAF inhibitors are not part of the treatment arsenal of patients with metastatic UM as BRAF mutations do not occur in UM [8,9]. Targeted therapy with MEK inhibitors is one of the few systemic treatments tested in a phase III clinical trial in UM but failed to show clinical benefit in combination with chemotherapy in the randomized setting [10]
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