Ipilimumab Improves Overall Survival in Patients with Metastatic Melanoma
There is no established standard of care for patients with metastatic melanoma, and no therapy has been shown to improve survival. Median overall survival has been estimated at less than 1 year (N Engl J Med 2004 Sep 2;351(10):998), while median survival with gastrointestinal metastases may be 4-6 months (Mayo Clin Proc 2006 Apr;81(4):511).
A recent phase III trial evaluated the effect of ipilimumab on survival outcomes in 676 previously treated patients with unresectable stage III or IV melanoma. Patients were randomized to receive 1 of 3 treatments: ipilimumab alone (dose 3 mg/kg), glycoprotein 100 peptide vaccine (GP100) alone, or ipilimumab plus GP100. Treatment was given once every 3 weeks for 1-4 cycles. Ipilimumab acts to block cytotoxic T-lymphocyte-associated antigen 4. GP100, which induces immune responses, was used as an active control.
Median overall survival was significantly higher for the ipilimumab group compared to GP100 (10.1 months vs. 6.4 months, p < 0.05) (level 1 [likely reliable] evidence). Overall survival was also higher for the combination group (10 months), but not significantly different from ipilimumab alone. There were no significant differences in median progression-free survival (about 2.8 months for all groups). Median follow-up was 17.2 months for the GP100, 21 months for the combination, and 27.8 months for ipilimumab alone. Overall 12-month survival ranged from 25.3% for GP100 alone to 43.6% for the combination and 45.6% for ipilimumab alone. Grade 3 or 4 immune-related adverse events were more frequent with ipilimumab than with GP100 alone (10%-15% vs. 3%).
Ipilimumab is not yet FDA approved (N Engl J Med 2010 Jun 5 early online).
