Results of a phase II trial reveal that ipilimumab, a drug belonging to a new class of immune-based therapies which alter the way the immune system fights cancer, may help shrink some tumors and may slow progression of secondary tumors in the brain (metastases) in some patients with advanced melanoma. The study is published Online First in The Lancet Oncology.
As many as half of all advanced melanoma patients will develop metastases. Furthermore, the average survival rate among these patients is just four months. According to the researchers, ipilimumab has already been demonstrated to improve overall survival.
Lead author of the study, Kim Margolin from the Seattle Cancer Care Alliance in the United States, said:
“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.
Our results show that anti-tumor activity, 2-year survival, and safety are similar to what has been reported in patients without brain metastases.”
Until now, no prospective study has been conducted on ipilimumab’s level of activity in individuals suffering with melanoma and brain metastases.
The researchers enrolled 72 patients with brain metastases to participate in the study:
- Cohort A contained 51 neurologically asymptomatic patients
- Cohort B contained 21 symptomatic patients receiving corticosteroids for clinical or radiological control of their brain metastases
The participants received 10 mg/kg of ipilimumab every three weeks for 4 doses. Participants who were stable at week 24 also received a maintenance dose every 12 weeks.
After three months of treatment, the authors found that 18% (9) of participants in cohort A, who were no dependent on steroids, achieved disease control (partial response or stable disease), while 1 (5%) patient in receiving corticosteroids in cohort B achieved a complete response.
The team found that long-term survival rates were comparable to that seen in patients without brain metastases, with almost one-third of those in both cohorts alive at 12 months. 26% of participants in cohort A were alive at 2 years compared with only 10% (2) of participants in cohort B.
According to the researchers, steroids may have a negative effect on ipilimumab activity, however, they warn that these data should not be over-interpreted.
They explain:
“This study design did not permit the assessment of other potentially unfavorable prognostic factors in cohort B such as tumor size, number and extent of peritumoral oedema and prior therapies.”
Immune-related adverse effects of ipilimumab included:
- dehydration
- diarrhea
- fatigue
- nausea
- rash
- pruritus
- hyperglycemia
These adverse effects are similar to those observed in earlier studies at the same dose and schedule.
One participant died of ipilimumab-related colitis. However, no excessive or unique CNS toxicities were observed in participants with brain metastases who received ipilimumab.
In an associated comment, Rosalie Fisher and James Larkin from the Royal Marsden Hospital, London, UK, explained:
“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.”
Written by Grace Rattue