Treatment for certain melanoma patients shows promise
To treat melanoma, the most serious type of skin cancer, doctors have turned to surgery, chemotherapy, radiation therapy, and even immunotherapy, among other treatment options.
Yet when it specifically comes to patients whose metastatic melanoma is linked with mutations in the BRAF gene, referred to as V600E or V600K, the best treatment option for those patients has been somewhat unclear — until now.
First-line treatment with two types of cancer drugs — dabrafenib, which inhibits BRAF, plus a MEK inhibitor drug called trametinib — was found to lead to long-term benefits in about one-third of patients who had melanoma with those gene mutations, according to a new study published in The New England Journal of Medicine on Tuesday. The study was simultaneously presented at the annual scientific meeting of the American Society for Clinical Oncology in Chicago.
About half of all melanomas have changes, or mutations, in the BRAF gene, according to the American Cancer Society. Melanoma cells with these mutations make an altered BRAF protein that helps them grow, and to treat this cancer, some drugs target that protein and others that are related, such as MEK proteins.
So if a melanoma patient has a BRAF mutation and needs targeted therapy to treat their cancer, they may receive a BRAF inhibitor drug, such as dabrafenib, plus a MEK inhibitor drug, such as trametinib — since combining those drugs appears to work better than using either one alone.
The new study involved analyzing data from two previous trials that assessed adult melanoma patients who were treated with dabrafenib and trametinib. Dabrafenib is sold as the brand name Tafinlar and trametinib is sold as the brand name Mekinist.
That data included 563 patients who were randomly assigned to receive dabrafenib twice daily plus trametinib once daily. Pharmaceutical companies GlaxoSmith-Kline and Novartis sponsored the trials.
By five years after first-line treatment with dabrafenib plus trametinib, the researchers found that 19% of the patients were progression-free and the overall survival rate was 34%.
By comparison, in the dabrafenib-plus-placebo group and in the vemurafenib group, the five-year overall survival rate was 27% and 23%, respectively.
“Our analysis demonstrates that first-line therapy with Tafinlar + Mekinist leads to five-year disease control in about one-fifth of the patients and five-year survival in about one-third of those treated,” Dr. Caroline Robert, head of the dermatology unit at the Institut Gustave Roussy in Paris who was first author of the study, said in a news release on Tuesday.
“While metastatic melanoma has historically had a very poor prognosis for patients, there are many reasons to be encouraged today. Our analysis demonstrates a clinically meaningful and positive impact on patient survival. These results show that targeted therapies may provide long-term survival and offer durable outcomes,” she said.
Some adverse events led to patients discontinuing the trial, which included fever, decreased pumping of blood in the heart, and increased levels of a certain enzyme in the liver and kidneys.
“This study addresses the half to 60% of patients with metastatic melanoma expressing BRAF V600E or V600. For those patients there has been a question mark,” said Dr. Otis Brawley, Bloomberg distinguished professor of oncology and epidemiology at Johns Hopkins University in Baltimore, who was not involved in the study.
“This study is well done and suggests that patients expressing the markers are more likely to benefit from the two targeted therapies in combination as a first treatment instead of the immunotherapy. It clarifies the question mark,” Brawley said.
“There is a second finding — the longer people survived the fewer relapsed. This suggests that a small proportion of these patients are cured of melanoma,” he said. “We in medical oncology are hesitant to use the word cure when talking about metastatic solid tumors but the fact that the long-term survival curves flatten is extremely encouraging.”
Last year the US Food and Drug Administration approved dabrafenib and trametinib in combination for the treatment of patients with melanoma with BRAF V600E or V600K mutations, as an adjuvant treatment, which means after initial treatment.
By Jacqueline Howard, CNN