New Treatment for Melanoma Shows Promise
Researchers may have discovered a new drug combination that could revolutionize the landscape of treatment for melanoma. More than 70% of clinical trial participants who received combined immunotherapy with ipilimumab and nivolumab showed benefits, according to a recent study.
“The magnitude of response is remarkable and has not been seen in oncology for decades,” says study co-author Montaser Shaheen, MD, a medical oncologist at the University of New Mexico Cancer Center and associate professor in the Department of Internal Medicine at UNM School of Medicine. “Thus, it will have a very positive impact on patient outcomes.”
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Shaheen and colleagues conducted a double-blind study of 142 patients with metastatic melanoma who had not previously received treatment. They investigated combined immunotherapy with two antibodies:
• Ipilmumab, which disables CTLA-4 receptors on the surface of melanoma cells, allowing the immune system to attack the tumor cells.
• Nivolumab, which blocks the PD-1 receptors on cytotoxic T-cells, allowing the immune system to fight against cancer cells.
The researchers randomized participants to receive ipilimumab combined with nivolumab or placebo once every 3 weeks for a total of four doses, followed by nivolumab or placebo every 2 weeks until the occurrence of disease progression or unacceptable side effects. While both drugs appear to work well individually, trial results showed they are particularly potent when combined.
Tumors shrunk in 61% of those treated with the combination of both drugs and disappeared completely in another 22% of patients who received the combination therapy. In comparison, standard treatment with chemotherapy typically causes tumors to shrink in only about 10% of melanoma patients.
Shaheen emphasizes two major improvements that this combined immunotherapy offers over traditional treatment options, such as chemotherapy:
• “A high percentage of patients benefit, with a 60% response rate plus a number of (patients achieved who) disease stabilization.”
• “The responses tend to be durable, unlike what we see with chemotherapy. This trial follow-up is not long enough to show durability, but we predict long responses from using the drugs as single agents.”
While Shaheen and his colleagues did not identify a subset of patients who would respond best to this treatment, he says there is no subset that does not benefit from the combination.
“A subsequently published sister trial suggested that the group of patients with PD-1 expression, the target of one of the drugs, may need only nivolumab and can be spared the toxicity of the combined regimen,” Shaheen says.
He and his colleagues concluded that the management of adverse events with the combination therapy suggests it can be used safely in a broad range of clinical settings.
“Other immune manipulations are also being pursued, such as the combination of the above drugs with IDO inhibitors, and other classes of drugs that break immune tolerance to tumors—hoping to ultimately help every patient with melanoma,” Shaheen says. “These drugs are also being tested in early stages on melanoma as well.”
—Colleen Mullarkey
Reference
Postow MA, Chesney J, Pavlick AC, Robert C, Grossmann K, McDermott D, et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. New Engl J Med. 2015 May 21;372:2006–17.