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.
Vemurafenib increases the effectiveness of a treatment that uses immune system cells modified to target cancer cells, according to a study in Cancer Research. When combined with vemurafenib, which targets melanomas with the most common BRAF mutations (V600), this immunotherapy treatment killed more melanoma cells in mice. The combination treatment was also more successful than vemurafenib alone. The researchers conclude that their work supports testing this combination treatment in people with melanomas that have BRAF V600 mutations.
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.
Primary source: http://www.nejm.org/doi/full/10.1056/NEJMoa1210093
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.
Primary source: http://www.nejm.org/doi/full/10.1056/NEJMoa1208958
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.
Primary source: http://jco.ascopubs.org/content/30/31/3819.abstract?sid=85400172-d445-4d85-958c-f7bda75450b6
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.
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.