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.
- metastatic melanoma
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.
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.
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.
Melanoma patients live longer when treated with ipilimumab than with an experimental tumor vaccine called gp100, according to a study by the German Institute for Quality and Efficiency in Health Care. People treated with ipilimumab lived 10 months, while those who were not lived 6.5 months. In addition, ipilimumab did not make people’s quality of life worse. People had the same symptoms—nausea, vomiting, digestive disorders, fatigue, and pain—whether they were treated with the drug or with a placebo.
A new drug combination could treat melanomas that resist therapy with a single drug, suggests research that appeared in Cancer Discovery on melanoma cells grown in the laboratory. The researchers tested melanoma cells that had BRAF mutations and resisted treatment with the BRAF inhibitor vemurafenib, and that had NRAS mutations, which resist many treatments. The most effective combination treatment was statins, which are commonly used to treat high cholesterol, but can also kill melanoma cells, and drugs that inhibit proteins called cyclin-dependent kinases, which are involved in cell division.
Despite promising results from small trials, a large clinical trial found that combining sorafenib with chemotherapy was no better than chemotherapy alone for melanoma patients. Sorafenib is FDA-approved for kidney and liver cancer that targets tumors by inhibiting the new blood vessels that help them grow and spread. However, this Journal of Clinical Oncology study also showed that the carboplatin/paclitaxel chemotherapy was surprisingly effective. This chemotherapy combination is now listed as a standard melanoma treatment by the National Comprehensive Cancer Network guidelines.
The experimental drug PV-10, which is injected directly into melanoma tumors, may work partly by boosting the immune system. To find out, researchers are launching a clinical trial to see if patients treated with PV-10 have immune biomarkers in their tumors and blood. The study will enroll up to 15 patients.