Immunotherapy Seen as Optimal First-Line Treatment for Advanced Melanoma

Immunotherapy Seen as Optimal First-Line Treatment for Advanced Melanoma

Patients diagnosed in the late stages of melanoma who have BRAF mutations should be given immunotherapy as a first-line treatment, according to a systematic review published in JAMA Oncology.

The study, “Systemic Therapy for Previously Untreated Advanced BRAF-Mutated Melanoma,” analyzed multiple first-line systemic treatment options for advanced BRAF-mutated melanoma, and found that BRAF/MEK-targeted therapies and PD-1 inhibitors significantly improved patients’ overall survival. PD-1 inhibitors, however, were favored as they carried a lower risk of serious adverse events.

“This is the first analysis to draw comparison between targeted and immune therapies for BRAF-mutated melanomas,” Feng Xie, an associate professor in the Department of Clinical Epidemiology and Biostatistics at McMaster’s Michael G. DeGroote School of Medicine, said in a press release. “Our results will help patients and clinicians choose treatments.”

Surgery is usually the standard treatment for patients with early stage melanoma, but people diagnosed in late disease stages are often not candidates for surgery. In these cases, drug therapy is the main course of treatment.

Advanced melanoma patients with BRAF mutations, which account for 40 percent to 60 percent of all melanoma cases, have a number of effective treatment options. These mainly fall under two classes: targeted therapies, which aim at specific proteins or pathways in cancer cells, leading to their death; and immunotherapies, which activate the immune system to recognize and kill cancer cells more effectively.

Which of these treatments is the optimal first-line therapy for advanced BRAF-mutated melanomas, however, is still not clear.

To address this, Xie and colleagues evaluated data from 15 randomized trials, published between 2011 and 2015, which included at least one intervention with a targeted (BRAF or MEK) or with an immune checkpoint (CTLA-4 or PD-1) inhibitor. The analysis included data from 6,662 BRAF-mutated advanced melanoma patients who received one of 10 treatment strategies.

Results showed that both BRAF/MEK inhibitors and PD-1 inhibitors led to similar improvements in overall survival, compared to all other treatments. BRAF/MEK inhibitors, especially, were associated with higher progression-free survival and overall response rates.

But the researchers found that chemotherapy and PD-1 inhibitors were associated with lower risk of serious adverse events, which supports the use of PD-1 inhibitors, such as Opdivo (nivolumab), as first-line therapy for patients with advanced melanoma and BRAF mutations. But they added that it should be used in circumstances where a quick response is not necessary.

“Compared with other treatments, BRAF/MEK and PD-1 inhibition significantly improved [overall survival],” they wrote. “The favorable safety profile of PD-1 inhibitors supports using this option as first-line therapy in circumstances where rapid response is not a priority.”

Added Xie: “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.”

According to the American Cancer Society, more than 76,000 new cases of melanoma will be diagnosed in the U.S. in 2016.


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