Metastatic uveal melanoma (mUM) is a rare disease with poor prognosis, hardly responding to systemic treatment. As the liver is the most common and prognostic relevant metastatic site, liver-directed therapies have come into focus.
A retrospective analysis was carried out in patients who were treated at our center between 2008 and 2017 receiving chemotherapy (1000 mg/m2 gemcitabine + 3500 mg/m2 treosulfan (GeT) on days 1 + 8, 4-week cycles) or transarterial chemoembolization (TACE, EmboCept® S microspheres + 50 mg cisplatin, every 4-6 weeks) as 1st-line therapy for mUM.
287 patients were treated for mUM in the time period, 93 received TACE and 82 GeT as 1st-line therapy. Patient characteristics differed in the metastatic pattern: patients receiving GeT having a significant higher rate of non-liver dominant metastatic disease compared to the TACE group (p < 0.001), whereas there was no difference in age, sex, DFI, laboratory values and percentage of liver involvement. Median overall survival (OS) in the GeT group was 11.3 vs. 8.4 months in the TACE group (p = 0.089), with a median progression-free survival (PFS) of 2.7 and 2.8 months respectively (ns). Overall response rate for GeT was 6.8% and disease control rate was 41.1%, for TACE 10.2% and 47.7% respectively (both ns). Age, sex, baseline laboratory values, PFS and percentage of liver involvement were significantly associated with OS in univariate analysis. Multivariate Cox regression analysis identified male sex, elevated bilirubin, GGT, ALP, percentage of liver involvement >50% and PFS ≤2.7 months as significant independent prognostic factors for shorter survival. The metastatic pattern and the type of treatment did not show to be significant prognostic factors.
Liver-directed therapies can improve response rates compared to systemic therapies and should be preferred in patients with liver-dominant metastatic pattern. However, PFS and OS remain poor and not significantly different between intrahepatic and systemic therapies. Further research should focus on developing new therapies based on a better understanding of the biology of these tumors.
Clinical trial identification
Legal entity responsible for the study
Charité Comprehensive Cancer Center, Charité - University Medicine Berlin.
Has not received any funding.
All authors have declared no conflicts of interest.