Ongoing Research Efforts in Metastatic Ocular Melanoma Could Shift Paradigm

Ragini Kudchadkar, MD

Advances have been few and far between in metastatic ocular melanoma, explained Ragini Kudchadkar, MD. However, as ongoing research unfolds, the field may be able to couple these findings with optimal patient selection to improve outcomes.

Patients with metastatic ocular melanoma have a poor prognosis. However, findings from a retrospective study showed that patients with ocular melanoma that is metastatic to the liver experienced prolonged progression-free survival (PFS) and overall survival (OS) if they had an ECOG performance status of 0 and received concurrent yttrium-90 (Y-90) and immunotherapy.

Among 24 patients who received immunotherapy within 3 months of undergoing Y-90, the median OS was 26 months versus 9.5 months for others (P = .014). For patients with an ECOG performance status of 0, the median OS was 26 months versus 5.5 months for others (P = .003). The median hepatic PFS was 10.3 months with Y-90 on concurrent immunotherapy versus 2.7 months in patients who received transarterial radioembolization only (P = .002).

“We're all trying to understand where liver-directed therapy lies in patients with melanoma, as we are combining these liver-directed therapies with traditional immunotherapies. The study shows that you can use liver-directed therapies along with other therapies to help improve outcomes for specific populations of patients,” said Kudchadkar, a co-author of the study.

In an interview with OncLive, Kudchadkar, associate professor, Department of Hematology and Medical Oncology, associate director, Hematology and Medical Oncology Fellowship Program-Clinical/Service, Emory University School of Medicine, Winship Cancer Institute, discussed the prognosis of patients with metastatic ocular melanoma and the work being done to define novel approaches in the space.

OncLive: Could you discuss the overall prognosis for patients with ocular melanoma?

Kudchadkar: Ocular melanoma is a different “beast” than cutaneous melanoma. The biology of ocular melanoma is very different in the sense that it primarily metastasizes to the liver, though it can go other places. Responses to traditional therapies, such as immunotherapy, are nowhere near the degree of responses in cutaneous melanoma, so patients’ prognosis is much more guarded. In ocular melanoma, we haven't made anywhere near the advancements we have made in cutaneous melanoma.

What is the state of treatment in ocular melanoma?

Right now, the primary treatment for patients with metastatic ocular melanoma is clinical trials. There are a lot of novel agents that are in the pipeline. There are 2 big phase III trials that are ongoing right now: one from [Delcath Systems with perfusion] with liver-directed chemotherapy and 1 with glycoprotein 100 versus standard of care, immunotherapy. Both trials are showing promise, and I'm very hopeful that there's more to come.

Could you discuss additional research in this space?

The 2 targets in clinical trials have been these novel immunotherapies. We’re also trying to target different gene mutations that lead to upregulation of the MEK pathway. Many MEK inhibitors have been tested, but we have yet to make a significant impact on the PFS of patients with this disease.

You co-authored a study on predictors of OS and PFS with Y-90 radioembolization in patients with ocular melanoma that is metastatic to the liver. What did the results of that study show?

The study showed that patients with metastatic ocular melanoma to the liver can undergo a liver-directed therapy to help control disease. Volume of disease and function of the liver are probably the biggest predictors of how well patients do with this procedure. Isolated metastases in patients with good overall liver function do the best.

Is there any other research in this space that you're excited about?

There has been a lot of excitement in skin cancers outside of melanoma. Traditionally, medical oncologists haven't been involved in the care of patients with Merkel cell carcinoma, squamous cell carcinoma, and basal cell carcinoma. It's very exciting to know that there are a lot of new immunotherapies and targeted therapies for patients with these diseases.

The multidisciplinary team should now include medical oncologists. We have a lot more options [beyond] surgery and radiation, which we perform with curative intent, [for] the small portion of patients that have more advanced disease.

The role of treatments in melanoma and non-melanoma skin cancers has dramatically improved as [have our biomarkers of response to these agents]. I'm really interested in biomarkers and how to address resistance to these therapies in advanced melanoma. Unfortunately, a group of patients still don’t respond to our therapies, [so we have more work to do].

Levey AO, Elsayed M, Lawson D, et al. Predictors of overall and progression-free survival in patients with ocular melanoma metastatic to the liver undergoing Y90 radioembolization. Cardiovasc Intervent Radiol. 2020;43(2):254-263. doi: 10.1007/s00270-019-02366-8.