Immunotherapies Should Be First-Line Treatment of High-risk Melanomas, Study Says

Immunotherapies Should Be First-Line Treatment of High-risk Melanomas, Study Says

Patients with advanced melanoma have improved survival rates with superior safety when treated with protocols that combine immunotherapy options, researchers recommended.

The study, “Systemic Therapy for Previously Untreated Advanced BRAF-Mutated Melanoma: A Systematic Review and Network Meta-Analysis of Randomized Clinical Trials,” published in JAMA Oncology.

Melanoma is an aggressive cancer that develops from the pigment-producing cells (melanocytes) in the skin. When detected early, it can be ably treated with surgery. But patients with highly aggressive melanomas or a late diagnosis are usually not good candidates for surgery, and drug therapy is the only treatment approach available.

According to Feng Xie, senior investigator and an associate professor in the Department of Clinical Epidemiology and Biostatistics at McMaster University, this study provided a first efficacy and safety comparison between two main therapeutic strategies — targeted and immune therapies — given patients with an aggressive subset of skin cancer, the BRAF-mutated melanomas, who have not yet received any treatment.

“Our results will help patients and clinicians choose treatments,” he said in a press release.

Mutations in a gene named BRAF can be found in around 40 percent to 60 percent of all malignant melanomas. These genetic alterations spur activity in the protein coded by this gene, inducing uncontrolled growth of malignant cells.

Patients with advanced BRAF-mutated melanoma can either undergo targeted therapy, which will inhibit the ability of the cancer cells to grow and spread, or immunotherapy, which stimulates the immune system to recognize and attack cancer cells.

The researchers analyzed the results of 15 clinical trials conducted between 2011 and 2015. They determined the benefits and harms of targeted or immune therapies in 6,662 patients with advanced BRAF-mutated melanomas, for whom surgery was not an option.

The study showed that the combination of  targeted therapies that inhibit the proteins BRAF and MEK — like two FDA-approved drugs, Tafinlar (dabrafenib) and Mekinist (trametinib) — and immunotherapies that specifically block a protein named PD-1 — like Opdivo (nivolumab) — are equally effective at improving overall survival.

The combined targeted therapies were most effective at extending the time in which the patients did not show symptoms of disease progression, while immunotherapy was associated with the lowest risk of life-threatening adverse events.

Given the safety profile of PD-1 inhibitors and beneficial results they showed in treating BRAF-mutated melanomas in this study, the authors propose that this treatment option should be used as first-line therapy in circumstances where quick action is not a priority.

“While the data in our study represents best available evidence, using more than one kind of immunotherapy shows promise in early outcomes in clinical trials and could change the treatment landscape once longer-term results are published,” Feng Xie concluded.

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