Improving survival in uveal melanoma

Improving survival in uveal melanoma

11 January 2017

With advancements in melanoma research in recent years, survival rates are skyrocketing for the first time ever. However, these promises of hope are not being seen in a rare form of melanoma, known as uveal melanoma, and researchers are desperately trying to uncover new ways to treat this disease.

Uveal melanoma is the most common form of cancer originating from the eye in adults. While there are effective treatments for early uveal melanoma, options are limited for patients who develop advanced (metastatic) disease. It is a very different disease to skin melanoma; it is caused by different gene mutations, is not linked to sun exposure, and responds differently to treatment. Unlike skin melanoma, the survival rate of patients with uveal melanoma – a form of ocular melanoma – has not changed over the last 35 years. It is an understudied cancer and further research is essential if survival rates are going to change.

“The drugs that are proving effective in skin melanoma have only minimal activity in uveal melanoma,” says Dr Matteo Carlino, medical oncologist at Melanoma Institute Australia (MIA).

In skin melanoma, response rates to anti-PD1 treatment are greater than 40%. However, when these same immunotherapy treatments are given to people with uveal melanoma response rates are only 3% to 4%.

“A lot of doctors use the drugs to treat uveal melanoma that we have for advanced skin melanoma, but this is because of a lack of options rather than evidence of success,” comments Dr Carlino. “We don’t know why, but there is a very small percentage of people with uveal melanoma who do respond to those treatments, and we need to find out why.”

A different disease

In addition to responding differently to treatment, uveal melanoma has different genetic mutations to skin melanoma.  BRAF and NRAS gene mutations, which are commonly seen in skin melanoma, are not seen in uveal melanoma. Uveal melanoma, however, is commonly associated with mutations in two genes (GNAQ and GNA11), offering hope that specific drugs can be developed to target these mutations.

Treating uveal melanoma

Following local treatment to the eye with surgery or radiotherapy, approximately half of all people with uveal melanoma will suffer a recurrence of the disease.

There is currently no standard treatment for advanced uveal melanoma, and so there is variable care between doctors. Some oncologists treat patients with advanced uveal melanoma in the same way as a patient with advanced skin melanoma. In selected patients, treatment directed at the liver – the most common site of recurrence – can be used.

“90% of people with uveal melanoma will have liver metastases as their site of recurrence; often it is their only site of recurrence,” says Dr Carlino.

Uveal melanoma clinical trials

“More research and trials are desperately needed to elevate survival rates, as has been the case with skin melanoma,” comments Dr Carlino.

To address this need in patients with uveal melanoma, MIA is running two new clinical trials investigating novel treatments for patients with metastatic uveal melanoma.

The Phase I study of a new targeted treatment for uveal melanoma, led by Dr Carlino at Westmead Hospital in affiliation with MIA, is currently recruiting [find out more]. The trial will test the safety, tolerability and efficacy of LXS196, an oral protein kinase C inhibitor, in patients with metastatic uveal melanoma. This drug has been specifically developed to target uveal melanoma mutations in the GNAQ and GNA11 genes.

There will also be a Phase III trial commencing at MIA in early 2017 to compare a new immunotherapy (called Immunocore) with chemotherapy (dacarbazine) in patients who have not received any other treatments. This is being investigated by Associate Professor Alex Guminski at MIA.

In addition to these clinical trials, laboratory studies to understand the response to these and other novel treatments for uveal melanoma will occur in Professor Helen Rizos’ MIA-affiliated research group at Macquarie University.

“The Phase I study will be the first time MIA has run a clinical trial in uveal melanoma and I’m excited to be part of it,” says Dr Carlino. “This is a world-wide trend: uveal melanoma has historically been under represented in clinical trials, but I think the tide is finally turning.”

If you are interested in participating in a clinical trial, ask your oncologist to contact Dr Carlino or A/Prof Guminski as strict eligibility criteria apply.