A study published last month in the Lancet Oncology shows that ipilimumab (Yervoy), an immunotherapy drug that was the first drug approved in metastatic melanoma in over a decade, also has activity in metastatic melanoma patients whose cancer has spread to the brain. Ipilimumab may also slow progression of brain metastases in some patients, according to the authors. Long-term survival of melanoma patients with brain metastases was comparable to survival of metastatic melanoma patients without brain metastases. Almost one-third of patients were alive at 12 months.
Ipilimumab was approved in March of last year by the US Food and Drug Administration for treatment of both newly diagnosed and previously treated patients with metastatic melanoma. The drug demonstrated an improvement in overall survival benefit. Ipilimumab works by inhibiting the immune system’s tolerance of cancerous cells, boosting the patient’s innate immune response to fight the cancer.
“Our results show that antitumor activity, two-year survival, and safety are similar to what has been reported in patients without brain metastases,” says Kim Margolin, MD, lead author of the study and a professor at the University of Washington School of Medicine, Seattle Cancer Care Alliance.
To date, there have been no effective systemic treatments for metastatic melanoma patients with brain metastases, according to Dr. Margolin. Furthermore, these patients do not always have clinical trial options as they are often excluded from trials because of their extensive disease. The majority of metastatic melanoma patients who develop brain metastases do not live long—the median overall survival is 4 months. Almost half of all patients with metastatic melanoma will develop brain metastases.
The Study Design and Results
A total of 72 patients were recruited to the trial; 51 patients were neurologically asymptomatic (cohort A) and 21 had neurological systems (cohort B) and received corticosteroids for clinical control of their brain metastases. Ipilimumab was given at a 10 mg/kg dose every 3 weeks for 4 doses, followed by a maintenance period of the same dose given at 12 week intervals for clinically stable patients.
In the asymptomatic cohort,18% (9 patients) had either a partial response or stable disease. Only 5% (1 patient) in the symptomatic cohort achieved disease control—a complete response.
Median overall survival was 7 months in cohort A and 3.7 months in cohort B. At 2 years, overall survival was 26% for patients who had asymptomatic brain metastases in cohort A. Overall survival for cohort B was 10% at 2 years.
The steroids taken by patients in cohort B may have had a negative effect on ipilimumab activity, the authors hypothesized. “The apparent low rate of benefit in this cohort suggests that further study is needed into patients with specific unfavorable prognostic factors and into avoidance of steroid use at the start of ipilimumab treatment,” the authors wrote.
Adverse events on ipilimumab were similar for patients with brain metastases as for metastatic melanoma patients without brain metastases treated in previous ipilimumab clinical trials. The drug is associated with immune-related side effects such as diarrhea, rash, fatigue, nausea, and pruritus. There were no unique central nervous system toxicities observed among the patients in the current phase II study.
“Generally melanoma patients that are candidates for ipilimumab end up having brain metastases. They are treated with ipilimumab after radiation and or surgery for their central nervous system disease,” explained Jeffrey Weber, MD, PhD, an experienced ipilimumab researcher at the Moffitt Cancer Center in Tampa, Florida.
In an accompanying editorial Rosalie Fisher, MD and James Larkin, MD, PhD from the Royal Marsden Hospital in London, highlighted that ipilimumab is a standard of care for metastatic melanoma and the current results in patients with brain metastases demonstrate that this subgroup of patients is just as eligible to receive ipilimumab. The researchers also stressed that new clinical trials should not exclude melanoma patients with brain metastases.