2854 - Real-world impact of immune checkpoint inhibitors in metastatic uveal melanoma

Background

Uveal melanoma (UM) is the most common intraocular malignancy. The disease is clinically and genetically distinct from cutaneous melanoma and shows a high rate of metastatic spread. As randomized clinical trials with immune checkpoint inhibitors (ICI) have not been performed in metastatic UM patients, we analysed the real-world outcomes in a nationwide population-based study.

Methods

Clinical data on patients with UM were extracted from the Danish Metastatic Melanoma database, a nationwide database containing unselected records of all Danish patients with metastatic melanoma. Diagnosis of primary UM was confirmed via the Copenhagen Epidemiological Uveal Melanoma Study database. Survival before (2011-2013, pre-ICI; n = 32) and after (2014-2018, post-ICI; n = 94) the approval of first-line treatment with ICI was analysed.

Results

Treatment and survival data were available from 126 metastatic UM patients. First-line treatment consisted of temozolomide in 28, ipilimumab in 24, pembrolizumab in 43 and the combination ipilimumab/nivolumab in 19 patients. Twelve patients did not receive any systemic treatment. No complete responses were observed. A partial response was observed in 7.0% of patients treated with pembrolizumab and in 21.1% treated with ipilimumab plus nivolumab. Median progression-free survival was 2.5 months for patients treated in the pre-ICI era compared to 3.7 months in the post-ICI era (HR 0.37; 95 CI 0.24-0.59; p < 0.01). The estimated 1-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 0.34-0.80; p < 0.01).

Conclusions

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. With the lack of therapies proven effective in randomized trials, these data support the current treatment with ICI in patients with metastatic UM.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Danish Melanoma Oncology Group.

Funding

The Danish Metastatic Melanoma database is supported by BMS, Roche, MSD and Novartis. K.F. Bol has received funding from the European Union (Marie Sklodowska-Curie grant).

Disclosure

K.F. Bol: Travel / Accommodation / Expenses: Roche. E. Ellebaek: Honoraria (self): BMS; Honoraria (self): Roche; Honoraria (self): Kyowa Kirin. M. Donia: Honoraria (self): BMS; Honoraria (self): Sanofi-Genzyme; Honoraria (self): MSD; Honoraria (self): AstraZeneca; Honoraria (self): Roche; Honoraria (self): Novartis. H. Schmidt: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): MSD; Honoraria (self), Advisory / Consultancy: Incyte; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Novartis. L. Bastholt: Advisory / Consultancy: MSD; Advisory / Consultancy: Incyte; Advisory / Consultancy: BMS; Advisory / Consultancy: Roche; Advisory / Consultancy: Eisai; Advisory / Consultancy: Novartis; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Bayer; Advisory / Consultancy: Amgen; Advisory / Consultancy: Swedish Orphan. I. Svane: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Novartis; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Incyte; Honoraria (self), Advisory / Consultancy: TILT Bio; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): BMS; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy, Shareholder / Stockholder / Stock options: IO Biotech. All other authors have declared no conflicts of interest.