Combination Treatments May Improve Survival for Patients with Metastatic Uveal Melanoma

A study published in Cancers suggested that the combination of liver-directed and newly developed systemic treatments may further improve the survival of patients with metastatic uveal melanoma. 

Additionally, researchers indicated that further investigation through prospective clinical trials is necessary to answer the question of whether a major contributing factor for improvement of survival is the shift of treatment modality from dacarbazine (DTIC)-based systemic chemotherapies to newly developed liver-directed treatments. 

“We recognized the poor prognosis associated with liver metastasis and we shift from systemic chemotherapies to the use of various liver-directed treatments,” Takami Sato, MD, PhD, director of the metastatic uveal melanoma program at the Sidney Kimmel Cancer Center, said in a press release. “We wanted to analyze patient outcomes before and after this shift.” 

In a retrospective analysis of patients with uveal melanoma and liver metastasis treated at Thomas Jefferson University Hospital, 80 patients treated between 1971 and 1993 (cohort 1), 198 patients treated between 1998 and 2007 (cohort 2), and 452 patients treated between 2008 and 2017 (cohort 3) were included. Each of the cohorts were similar in regard to demographic and eye tumor characteristics, except for age at eye diagnosis. Overall, 70% of patients in cohort 1 only received systemic therapies as their treatment modality for liver metastasis, while 98% of patients in cohort 2 and 3 received liver-directed treatment either alone or in addition to systemic therapy. 

The median mets-to-death overall survival (OS) rate was shortest in cohort 1 (5.3 months, 95% CI: 4.2-7.0), longer in cohort 2 (13.6 months, 95% CI: 12.2-16.6), and longest in cohort 3 (17.8 months, 95% CI: 16.6-19.4). Median eye tx-to-death OS was shortest in cohort 1 (40.8 months, 95% CI: 37.1-56.9), and similar in cohort 2 (62.6 months, 95% CI: 54.6-71.5) and 3 (59.4 months, 95% CI: 56.2-64.7). 

Moreover, in all 3 cohorts, patients who received liver-directed as well as systemic treatments, consecutively or in combination, showed survival benefit over “systemic treatment alone” or “liver-directed treatment alone.” 

“The interpretation of this finding is solely speculative; however, an increase in mets-to-death OS in proportion to an increase in the fraction of ‘liver-directed + systemic’ as treatment modalities in cohort 2 and 3 might indicate the potential role of newly emerged immunotherapies in prolonging survival of (uveal melanoma) patients with liver metastasis,” the authors wrote.

Notably, with the recent innovations in systemic therapies, researchers suggested that we are heading toward another paradigm shift on treatment of metastatic uveal melanoma. Newer systemic therapies under investigation, like IMCgp100 (Tebentafusp), that have indicated possible survival benefits in metastatic uveal melanoma, could be combined with liver-directed therapies to further improve the outcome of patients with uveal melanoma who also have hepatic metastasis.  

Currently, there is no FDA approved treatment for metastatic uveal melanoma and overall outcomes tend to be poor for patients who develop liver metastasis. 

Reference:

1. Seedor RS, Eschelman DJ, Gonsalves CF, et al. An Outcome Assessment of a Single Institution’s Longitudinal Experience with Uveal Melanoma Patients with Liver Metastasis. Cancers. doi:10.3390/cancers12010117.

2. Shift in treatment modalities associated with improved outcomes in uveal melanoma patients with liver metastasis [news release]. Philadelphia, Pennsylvania. Published February 3, 2020. jefferson.edu/about/news-and-events/2020/2/Shift-in-treatment-associated-with-improved-outcomes-in-uveal-melanoma-patients-with-liver-metastasis.html. Accessed February 5, 2020.