Early research led by investigators at Memorial Sloan Kettering cautions against combining ipilimumab and vemurafenib for the treatment of metastatic melanoma.
Recently, major strides have been made in the treatment of advanced melanoma with the approval of two new drugs: an immunotherapy agent called ipilimumab (YervoyTM) and vemurafenib (Zelboraf®), a drug that is effective in patients with a mutation in a gene called BRAF.
The two drugs were the first in more than a decade to show an increase in overall survival in patients with the disease. Research teams at Memorial Sloan Kettering were instrumental in the development and clinical trials of both, and after the drugs received approval by the US Food and Drug Administration, investigators had a keen interest in studying them in combination to achieve potentially better outcomes.
In a report published on April 4 in the New England Journal of Medicine, medical oncologist Jedd Wolchok, medical oncologist and research fellow Margaret Callahan, and colleagues from Memorial Sloan Kettering, Dana Farber Cancer Institute, and the University of California, Los Angeles, found that combining the drugs and administering them at the same time to a small group of patients led to more side effects than were expected. These side effects included changes in liver function that were significant enough to stop the phase I clinical trial — but were completely reversible.
“We felt this information was important for medical oncologists to have because both ipilimumab and vemurafenib are presently approved by the FDA and widely available,” Dr. Callahan says. “We felt this initial experience suggested that the two drugs cannot be safely combined, at least on the schedule we tested.”
Dr. Wolchok adds, “We also took this opportunity to begin to study this in the laboratory and are now beginning to investigate alternatives to the dosing schedule. Perhaps the medicines could be used in sequence rather than at the same time.”
The Memorial Sloan Kettering team will also move forward with clinical trials focusing on new approaches of combining ipilimumab with other drugs for patients with advanced melanoma.