Preserving Vision in Uveal Melanoma (Podcast)

Uveal melanoma is a rare disease that affects the pigmented cells inside the eye and can spread to other parts of the body. Cleveland Clinic sees roughly 100-150 of these cases a year. As new therapies move through clinical trials, the management of uveal melanoma is entering a period of significant change.

In a recent episode of Cleveland Clinic’s Cancer Advances podcast, Director of Ophthalmic Oncology Arun Singh, MD, discussed how tumor size impacts treatment approaches and the risk of disease metastasis. He shared three novel approaches being studied to:

• Evaluate therapies that are radiation-dependent
• Providing neoadjuvant therapy to shrink tumors prior to surgery
• Inject medications to prevent vision loss from radiation

Click the podcast player above to listen to the episode now, or read on for a short edited excerpt. Check out more Cancer Advances episodes at clevelandclinic.org/podcasts/cancer-advances or wherever you get your podcasts.

Excerpt from the podcast

Dale Shepard, MD, PhD:

Can you tell me about some of the trials that are going on?

Arun Singh, MD:

We are seeking treatments that are not radiation-dependent to avoid radiation retinopathy or radiation vision loss. So that's an Aura CoMpass trial ongoing, randomized trial now Phase 3, and previously Phase 2 studies have been very encouraging.

We are trying to use viral capsid-like material that's injected into the eye, followed by laser treatment, to achieve local control for small growing melanomas. So very specific criteria, and the trials should be finished by the end of this year and another maybe two years before the readout to see the outcomes of this randomized trial. At least here at Cleveland Clinic Cole Eye, we have patients that are enrolled in this trial and that's ongoing. So that's to avoid radiation altogether.

And the second trial is to identify patients who are at high risk of vision loss from radiation because of the size of the tumor or the proximity to the macular or the vision area of the retina. And in those patients, we can randomize them also into a trial for prevention of vision loss from radiation. So we know they're at the risk of it and then we can inject certain drugs in the eye to prevent vision loss from radiation. Here they get the benefit of good control from radiation, which we know is highly effective, 99%, and at the same time try to mitigate the main side effect, which is the radiation retinopathy.

And the third trial, which is also interesting, is a novel approach where we are trying to reduce the tumor size. We never really had any medications or drugs that will reduce the tumor within the eye. So here we are using neoadjuvant, or before primary treatment, and oral medication, darovasertib, which can reduce tumor by almost 50% maybe in 70, 80% of cases.

The drug is a pill and the tumor is monitored and there's a reduction in size. And as long as there's a reduction, you can continue the medication for maybe up to even six months. And then very likely the tumor has become smaller than large. It was large, that becomes medium. Then you could do radiation treatment. And if it was medium-sized tumor, would get smaller within its own group and then the radiation collateral damage would be minimized because the tumor size has become small.

So one is to avoid radiation altogether, one trial, that's the Aura trial. Second is the DRCR trial where we're trying to keep the radiation, but minimize the radiation damage by preventing using certain adjuvant medications. And third is to reduce the tumor, avoid enucleation. And if it's a medium size, very likely reduce the risk of radiation retinopathy. So all three approaches are ongoing and it's exciting.