Ipilimumab looks promising in shrinking/slowing melanoma brain metastases

Emerging uses of FDA Approved Drugs – by Bruce Sylvester – Researchers from a phase 2 study published  on March 27 in The Lancet Oncology  report that ipilimumab, which improves overall survival in patients with advanced melanoma, could shrink some brain tumors and slow metastasis in some patients.

As background, the authors noted that up to half of all patients with advanced melanoma develop secondary brain tumors, and the average survival among such patients is only 4 months.

“Currently, there is no effective systemic treatment for melanoma brain metastases, and patients whose cancer has spread to the brain are frequently excluded from promising clinical trials,” said lead author Kim Margolin, MD, Seattle Cancer Care Alliance, Seattle, Washington. “Our results show that anti-tumour activity, 2-year survival, and safety are similar to what has been reported in patients without brain metastases.”

Dr. Margolin and colleagues recruited 72 patients with brain metastases and separated them into 2 cohorts: neurologically asymptomatic patients (cohort A; n = 51) and symptomatic patients receiving corticosteroids for clinical or radiological control of their brain metastases (cohort B; n = 21). The subjects  received ipilimumab 10 mg/kg every 3 weeks for 4 doses, with maintenance treatment every 12 weeks for patients who were clinically stable at week 24.

After 3 months of treatment, 9 patients (18%) in cohort A, who were not corticosteroid-dependent, achieved disease control (partial response or stable disease), while 1 (5%) patient in cohort B achieved a complete response.

Long-term survival was similar to that reported for patients without brain metastases, with almost one-third of patients in both cohorts alive at 12 months. In cohort A, 26% of patients were alive at 2 years while only 2 (10%) patients in cohort B were still alive at 2 years.

In an accompanying commentary, Rosalie Fisher, MD, and James Larkin, MD, Royal Marsden Hospital, London, United Kingdom, said, “Ipilimumab is now a standard of care for advanced melanoma and, in our view, these data show that the presence of brain metastases should not prevent the use of ipilimumab. The era in which patients with brain metastases are excluded from clinical trials must end. Brain metastases are a major problem for patients with advanced melanoma and their families and we need to offer them active drugs as a matter of urgency.”