For patients with uveal melanoma, the most common eye cancer in adults, survival outcomes have improved in recent years, after treatment modalities shifted from systemic to liver-directed therapies
The finding comes from researchers at the Thomas Jefferson University in Philadelphia, Pennsylvania, and was presented at the recent American Society of Clinical Oncology (ASCO) 2018 annual meeting.
"Our study is the largest, real-world data showing improvement of the outcomes of metastatic uveal melanoma patients over the last 50 years with newer liver-directed treatments, including radioembolization," lead author Rino S. Seedor, MD, told Medscape Medical News.
During the past 50 years, treating liver metastases in uveal melanoma has been a journey, she explained, from systemic chemotherapy in the 1970s to transarterial chemoembolization (TACE) with 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU), drug-eluting beads with doxorubicin, immunoembolization, and radioembolization.
For their study, Seedor and colleagues carried out a retrospective chart review of consecutive patients with uveal melanoma with liver metastasis who were treated at their institution. They grouped patients into those treated between 1971 and 1993 (cohort 1; n = 101) and those treated between 2000 and 2017 (cohort 2; n = 655).
"Novel liver-directed therapies were being developed between 1993 and 1999, and these years represent the transitional years. Including patients from these years would have provided mixed results," Seedor said.
Eye tumor characteristics were similar across the two cohorts (location of the tumor, maximum tumor diameter, thickness, and T stage). First eye treatment included enucleation, radioactive plaque, and external radiotherapy.
For liver metastases, 81% of patients in cohort 1 received systemic therapy; in cohort 2, 88% of patients first received liver-directed therapies, which included immunoembolization (n = 270), TACE (n = 131), drug-eluting beads with doxorubicin (n = 42), and radioembolization (n = 36).
Median overall survival (OS) from metastases to death improved from 4.8 months for patients in cohort 1 to 16.8 months for those in cohort 2 — an approximately fourfold increase (P = .0271). Median OS from uveal diagnosis to death was also prolonged — from 3.4 years for patients in cohort 1 to 5.0 years for those in cohort 2 (P < .0001).
After adjusting for variables such as year of diagnosis and time from diagnosis of primary uveal melanoma to liver metastasis, patients in cohort 1 were at a 77% increased risk for early death after the development of liver metastasis compared to patients in cohort 2 (hazard ratio, 1.77; P = .0271).
The investigators also noted some of the limitations of their study — it was a single-institution study, a retrospective analysis, and cohort 1 had a small number of patients. The missing information for the period between 1993 and 2000 represented the transition between systemic to liver-directed therapies, they commented.
Takami Sato, MD, medical oncologist and senior author on the study, pointed out that liver-directed therapies are undertaken at institutions in which there is the collaboration between medical oncologists and interventional radiologists.
Most institutions that currently provide systemic treatment for liver metastases use checkpoint blockades either through a single agent, which provides responses of less than 5% or in combination, which provides response rates between 10% and 15%.
He indicated that newer systemic therapies under investigation, such as IMCgp100, which have shown the potential survival benefit, could be combined with the liver-directed therapies to further improve the outcome of uveal melanoma patients with hepatic metastases.
Prolonged Survival With Radioembolization
Another presentation at the meeting, from researchers at the same institution, gave details on radioembolization for the treatment of liver metastases, which showed that it could lead to prolonged survival.
Gonsalves said that liver-directed treatment should be considered in all cases of liver metastases, and multidisciplinary collaboration is essential. "At our institution, medical oncology and interventional oncology have weekly clinics and weekly conferences where we review uveal melanoma cases," she said.
Gonsalves said that radioembolization is a one-time treatment, unlike other liver-directed treatments, which are often given multiple times until disease progression. "In radioembolization, we treat once, and then we watch," she said