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.
- BRAF L597
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.
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.
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.
Primary source: http://www.nejm.org/doi/full/10.1056/NEJMoa1203421
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.