TAMPA, Fla. — Patients with advanced melanoma and disease that has spread to the brain have limited treatment options and may survive only four to five months. But Moffitt Cancer Center researchers hope to improve the prognosis of these patients. They participated in a clinical trial to determine if drugs that reactivate the immune system to target cancer cells are effective treatment options for melanoma patients with brain metastases. The study published online today in The New England Journal of Medicine.

Patients with advanced melanoma commonly develop metastatic disease in the brain.  Approximately one-third of melanoma patients with advanced disease have brain metastases at diagnosis, and up to 75 percent of these patients have brain metastases at the time of death. New radiation therapy approaches can reduce disease burden in the brain; however, these treatment options are ultimately not effective and may not increase overall survival.

The immune-activating drugs ipilimumab and nivolumab, which target CTLA-4 and PD-1, respectively, are approved to treat several types of cancer, including melanoma. A previous study has shown that ipilimumab plus nivolumab in combination is an effective treatment option in advanced melanoma patients, but has a high incidence of side effects. However, the study did not include patients with untreated brain metastases.

Researchers at 28 cancer centers throughout the United States, including Moffitt, participated in a study to determine if the combination of ipilimumab and nivolumab is effective in untreated melanoma patients with metastatic brain disease who did not have symptoms related to the brain metastases. Out of 94 patients who were eligible for evaluation, 54 (57.4 percent) achieved a clinical benefit in the brain for at least six months, including 24 patients with a complete response, 28 with a partial response and two with stable disease. 

The patient responses occurred rapidly after treatment and were long-lasting, with a median time to response of 2.3 months, and 64.2 percent and 59.5 percent of patients maintaining a response without disease progression at six months and nine months, respectively. The researchers also found that the drug combination was more effective in patients who had higher levels of tumor expression of PD-L1.

The researchers report that the drug combination was safe in this patient population. The number and types of adverse events were similar to those reported previously for the combination of nivolumab and ipilimumab in melanoma patients without brain metastases. Grade 3 or 4 treatment-related adverse events occurred in 55 percent of patients, with the most common being alterations in liver enzyme levels. The most common any-grade treatment-related adverse event in the central nervous system was headache, which was reported in 22 percent of patients, with 3 percent experiencing grade 3 or 4 headache. Other grade 3 or 4 neurologic adverse events were brain edema in two patients, and intracranial hemorrhage, peripheral motor neuropathy and syncope in one patient each.

“Our results demonstrate that nivolumab combined with ipilimumab is a safe and effective treatment option that should be considered as first-line therapy for patients with asymptomatic, untreated melanoma brain metastases. This combination immunotherapy may delay or preclude the need for radiotherapy and/or surgery,” explained Peter Forsyth, M.D., chair of the Neuro-Oncology Program at Moffitt.  

“A multidisciplinary approach is critically important in the management of melanoma brain metastases so that we can continue to improve the outcome for our patients.  Our interdepartmental collaboration was key to the success of this trial, which may set a new systemic therapy standard for metastatic melanoma to the brain,” added Nikhil Khushalani, M.D., vice chair of the Cutaneous Oncology Program at Moffitt.

The study was funded by Bristol-Myers Squibb.

About Moffitt Cancer Center
Moffitt is dedicated to one lifesaving mission: to contribute to the prevention and cure of cancer. The Tampa-based facility is one of only 49 National Cancer Institute-designated Comprehensive Cancer Centers, a distinction that recognizes Moffitt’s scientific excellence, multidisciplinary research, and robust training and education. Moffitt is a Top 10 cancer hospital and has been nationally ranked by U.S. News & World Report since 1999. Moffitt devotes more than 2 million square feet to research and patient care. Moffitt’s expert nursing staff is recognized by the American Nurses Credentialing Center with Magnet® status, its highest distinction. With more than 6,000 team members, Moffitt has an economic impact in the state of $2.1 billion. For more information, call 1-888-MOFFITT (1-888-663-3488), visit MOFFITT.org, and follow the momentum on FacebookTwitter and YouTube