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document
Ipilimumab efficacy and safety in patients with advanced melanoma : a retrospective analysis of HLA subtype from four trials . Ipilimumab is a fully human , monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 to potentiate an antitumor T-cell response . This agent improved overall survival in a phase III trial in previously treated patients with advanced melanoma . Because the mechanism of action for ipilimumab is thought to be HLA independent , most trials enrolled patients without regard to HLA subtype . However , enrollment in the phase III trial was restricted to class-I HLA-A*0201-positive patients because two of the three arms contained an HLA-A*0201-restricted gp100 vaccine . HLA typing was also performed prospectively in several phase II trials and was available for 93.5 % of patients . In this retrospective analysis , pooled efficacy and safety data are presented according to HLA-A*0201 status and dose from pretreated patients randomized to 0.3 , 3 , or 10 mg/kg ipilimumab in four phase II trials . Median overall survival ( OS ) was similar for the 187 HLA-A*0201-positive [ 9.3 months , 95 % CI ( confidence interval ) 7.4-11.5 ] and 266 HLA-A*0201-negative patients [ 11.4 months , 95 % CI 9.3-15.1 ] randomized to ipilimumab at all doses across the four phase II trials . These data are comparable to the OS for the 137 HLA-A*0201-positive patients randomized to ipilimumab in the phase III study [ 10.1 months , 95 % CI 8.0-13.8 ] . Ipilimumab-induced adverse events and immune-related adverse events ( skin , gastrointestinal , hepatic , other ) also occurred at similar frequencies among patients in the phase II and III trials , regardless of HLA-A*0201 status . These findings support the hypothesis that ipilimumab-treated patients with advanced melanoma have similar outcomes regardless of their HLA-A*0201 status .
47838
Intervention_Pharmacological
Ipilimumab
47839
Intervention_Pharmacological
Ipilimumab
47840
Intervention_Pharmacological
ipilimumab
47841
Intervention_Pharmacological
HLA-A*0201-restricted gp100 vaccine
47842
Intervention_Pharmacological
Ipilimumab-induced
47843
Intervention_Pharmacological
ipilimumab-treated
47844
Outcome_Other
pooled efficacy and safety data
47845
Outcome_Mortality
Median overall survival ( OS )
47846
Outcome_Mortality
OS
47847
Outcome_Adverse-effects
Ipilimumab-induced adverse events and immune-related adverse events ( skin , gastrointestinal , hepatic , other )
47848
Participant_Condition
advanced melanoma
47849
Participant_Condition
previously treated
47850
Participant_Condition
advanced melanoma
47851
Participant_Condition
class-I HLA-A*0201-positive
47852
Participant_Condition
pretreated
47853
Participant_Condition
HLA-A*0201-negative
47854
Participant_Sample-size
137
47855
Participant_Condition
HLA-A*0201-positive
47856
Participant_Condition
ipilimumab-treated