People with melanoma lived longer when treated with a combination of dabrafenib (a BRAF inhibitor) and trametinib (a MEK inhibitor) than with dabrafenib alone, according to research in The New England Journal of Medicine. The study included 247 people with melanomas that had BRAF V600E mutations. Treatment with both drugs increased survival to 9.4 months, compared to 5.8 months with dabrafenib alone. In addition, tumors were not evident or shrank considerably in 76% of people treated with both drugs compared to 54% of those treated with dabrafenib alone.
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.
A melanoma patient treated with vemurafenib also developed leukemia temporarily, according to a case report in The New England Journal of Medicine. This drug was already known to cause squamous cell skin cancers in some people with melanomas that have BRAF mutations. Vemurafenib activates proteins called extracellular signal-regulated kinases (ERK), which are involved in cell division and can lead to cancer in cells that have RAS mutations. The leukemia in the vemurafenib-treated patient had a RAS mutation and disappeared after treatment ended. The patient’s melanoma tumors, which did not have a RAS mutation, shrank during treatment.
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 blood test could show whether melanomas are likely to return in patients who are clinically free of the disease, according to a study in the Journal of Clinical Oncology. Cancer cells that break off tumors can enter blood vessels; this test identifies three tumor cell biomarkers in blood. The researchers periodically tested blood samples of 322 patients and found those with up to one cancer biomarker were more likely to be melanoma-free compared to those with two or more cancer biomarkers (73% vs 59%). This test could show which patients would benefit from aggressive treatments.
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.
Treatments that target a protein called MEK could work better when combined with drugs that inhibit a protein called SMURF2, according to research in the British Journal of the National Cancer Institute. MEK is involved in cell division and can be activated by BRAF and NRAS mutations. However, melanomas often resist MEK inhibitors. The researchers found that MEK inhibitors made melanoma cells grown in the laboratory produce too much of a protein called SMURF2. This in turn led to overproduction of another protein called MITF, which protects melanomas against MEK inhibitors. When treated with both a MEK inhibitor called selumetinib and a SMURF2 inhibitor, tumor growth was suppressed by 98% in mice.
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 impressive, but still short-term, benefits of vemurafenib for melanoma patients may not justify the hefty cost to a Massachusetts Medicaid program, according to an analysis presented at an American Society of Health-System Pharmacists meeting. Vemurafenib targets the most common mutation of BRAF, which is one of the genes that is most often abnormal in melanomas. The analysis noted that vemurafenib boosted 6-month survival rates over those of the conventional chemotherapy drug dacarbazine (84% and 64%, respectively). However, vemurafenib is also more expensive than dacarbazine, with relative per patient costs estimated at $9,995 and $1,811 per month, respectively.