Ipilimumab Demonstrates Activity in Patients With Brain Metastases

Ben Leach
Published: Tuesday, May 22, 2012
Dr. Agarwala

Sanjiv S. Agarwala, MD
Professor of Medicine
Temple University School
of Medicine
Chief, Oncology /Hematology
St. Luke’s Hospital and Health Network Bethlehem, PA

Ipilimumab (Yervoy; Bristol-Myers Squibb) generates antitumor activity in some patients with advanced melanoma whose disease has metastasized to the brain without resulting in unexpected toxicities, according to the results of a study published online in The Lancet Oncology in March.

Whether the findings will make an immediate impact on clinical decisions is doubtful, however, because oncologists may already be considering the drug for patients with brain metastases, according to Sanjiv S. Agarwala, MD.

The phase II study, conducted in 10 centers in the United States, is believed to be the first to specifically examine the effects of ipilimumab on patients with brain metastases in a prospective manner, although such metastases pose a significant problem with melanoma. The frequency of brain metastases in advanced melanoma ranges from 10% to 50%, with autopsy results suggesting the incidence could be as high as 66% to 70%, investigators noted in the study.

“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 A. Margolin, MD, Seattle Cancer Care Alliance, Washington, in a statement.

In all, 72 patients with advanced melanoma and disease metastasized to the brain were enrolled in the phase II study. They were divided into two cohorts: cohort A, with 51 patients who were neurologically asymptomatic and were not receiving corticosteroids, and cohort B, with 21 patients who were symptomatic and on a stable dose of corticosteroids. (Figure)

Figure. Study of Ipilimumab to Treat Melanoma in Patients With Brain Metastases

Figure of study results

ECOG indicates Eastern Cooperative Oncology Group.

Both groups received ipilimumab during a 12- week period in 4 doses of 10 mg/kg administered intravenously once every 3 weeks.

After the treatment, 9 patients in cohort A (18%) and 1 patient in cohort B (5%) exhibited disease control. In the brain alone, 12 patients in cohort A (24%) and 2 in cohort B (10%) achieved disease control.

The most common grade 3 adverse events were diarrhea (12%) and fatigue (12%) in cohort A, and dehydration (10%), hyperglycemia (10%), and increased concentrations of serum aspartate aminotransferase (10%) in cohort B. One patient in each cohort experienced grade 4 confusion. The data suggest that patients who received ipilimumab were able to tolerate the drug.

“We believe that these data are sufficient to support use of ipilimumab in selected patients with brain metastases, particularly metastases that are small and asymptomatic,” the researchers concluded. “Additionally, we have provided safety and initial efficacy data that could serve as the foundation for future trials of combinations of ipilimumab and radiotherapy, other immunotherapies, or possibly molecularly targeted agents.”

Agarwala said, however, that the study might make little or no difference in how patients with advanced melanoma are treated because it does not provide additional information of immediate benefit. He also said the size of the study population was too small to draw meaningful conclusions on which to base treatment decisions.

At the same time, Agarwala noted that ipilimumab has already been approved to treat patients with unresectable or metastatic disease, so although patients with brain metastases may have been previously excluded from clinical trials, those patients can still be prescribed the drug. In fact, Agarwala said, ipilimumab has already demonstrated activity in patients with brain metastases in studies performed prior to the drug’s approval last year.

“Prescribing physicians should feel free to use ipilimumab in these patients,” Agarwala said. “I’m not going to be changing my treatment paradigm as a result of this study.”

Bristol-Myers Squibb sponsored the clinical trial (NCT00623766).


Margolin K, Ernstoff MS, Hamid O, et al. Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial [published online ahead of print March 27, 2012]. Lancet Oncol. 2012;13(5):459-465. doi:10.1016/S1470-2045(12)70090-6.



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