Melanoma of the Eye: Better Diagnostics and Future Treatments

Laitr Keiows / Wikimedia Commons Laitr Keiows / Wikimedia Commons

Ocular melanomas, or melanomas found in the eye, are fairly infrequent, but they are the most common type of eye tumor. In the U.S., there are about 2,000 cases diagnosed each year. They occur within one of the three parts of the eye: the iris, the choroid, or the ciliary body. Collectively, these are known as the ‘uvea,’ hence an alternative name for this cancer: uveal melanoma. Continue reading…

First Drug that Treats Melanomas in the Eyes

About half of melanomas that start in the eye spread to other parts of the body, usually killing people within a year. But while there are a variety of therapies for melanomas in the skin, those in the eyes are biologically distinct and there has been no good way to treat them—until now. A clinical trial of 157 people showed that a drug called selumetinib can shrink melanomas of the eye, which form in a layer called uvea that includes the iris. Selumetinib is a MEK inhibitor that targets the most common uveal mutations (GNAQ and GNA11). The researchers found that tumors shrank in in half of those treated with selumetinib and did not grow again for twice as long compared to those treated with standard chemotherapy (an average of 16 vs 7 weeks). This work was presented at the American Society of Clinical Oncology’s 2013 meeting.

Ipilimumab Could Treat Small Melanomas in the Brain

A study in The Lancet shows that the drug ipilimumab could treat melanomas that have spread to the brain, particularly in people who do yet not have neurological symptoms. Of 51 such patients treated with ipilimumab, 12 had tumors in the brain that shrank or did not get worse and 14 had tumors outside the brain that shrank or did not get worse. Ipilimumab (Yervoy) is an immune system booster that the FDA has approved for treating advanced melanomas.

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Drug Targets Two Common Melanoma Mutations

An experimental drug could help control some melanomas that have BRAF or NRAS mutations, according to a report at an American Society of Clinical Oncology meeting. Tumors shrank or did not get worse in 8 out of 35 patients with the most common BRAF mutation (V600E), and in 6 out of 28 patients with NRAS mutations. This is the first targeted treatment for melanomas that have NRAS mutations. BRAF and NRAS mutations can activate a protein called MEK that is involved in cell division. The experimental drug, which is called MEK162, is a MEK inhibitor. The side effects of MEK162, which included diarrhea, rashes and swelling, were manageable.

Dabrafenib May Shrink Melanomas in the Brain

An early stage clinical trial suggests that dabrafenib, a BRAF inhibitor, could treat melanomas that have spread to the brain. The study, reported in The Lancet, included 10 people with brain metastases of melanomas that had BRAF mutations. Tumors shrank in 9 patients and were not evident in 4 patients. This is a surprise because the drug had not been expected to cross the blood-brain barrier effectively. Indeed, melanoma patients with brain metastases have been routinely excluded from previous trials of vemurafenib (Zelboraf) and other BRAF inhibitors.

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Trametinib Outperforms Chemotherapy for Melanomas with BRAF Mutations

A New England Journal of Medicine study reports a promising new approach to treating melanomas with BRAF mutations, which often respond to BRAF inhibitors for just a short time. Melanoma patients treated with trametinib were stable (ie, did not get worse) for three times longer than those treated with dacarbazine, a conventional chemotherapy drug (4.8 vs. 1.5 months, respectively). Trametinib inhibits MEK, a protein that is activated by BRAF and is involved in cell division. The drug’s most common side effects were rash, diarrhea, and swelling in the legs, which could be controlled by periodically adjusting the dose.

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New Melanoma Mutation Frequent Enough for Routine Screening

Researchers identified a new mutation (BRAF L597) in a melanoma patient and then tested for it in 49 other melanomas that had no known cancer-linked mutations, which account for about half of all melanomas. They found that BRAF L597 occurred in 4% of the other melanomas tested. The study, which appeared in Cancer Discovery, also showed that tumors with this mutation respond to a MEK inhibitor called TAK-733. The existence of a targeted treatment, coupled with the new mutation’s relatively high incidence, lead the researchers to suggest routinely screening melanomas for BRAF L597.

UK Health Institute Approves Vemurafenib and Ipilimumab for Melanomas

The National Institute for Health and Clinical Excellence (NICE) recommends giving people in England and Wales access to vemurafenib and ipilimumab via the National Health Service (NHS). The FDA has already approved these drugs for treating metastatic melanoma in the U.S. Initially, the cost of these treatments was a stumbling block in the UK and the watchdog institute’s recommendation comes with the caveat that manufacturers must provide a discount to the NHS.

Vemurafenib Extends Life up to 3 Years in Melanoma Trial

An ongoing clinical trial found that 26% of melanoma patients treated with vemurafenib (Zelboraf®) were alive at 3 years—far longer than the average survival time of 9 months with conventional chemotherapy. Vemurafenib is a BRAF inhibitor and this trial includes 32 people with the most common BRAF mutation (V600E). In addition, five people survived at 3 years and 4 months; three of them had no evidence of disease.