Ipilimumab

Previously treated patients. A total of 676 patients with previously treated, unresectable stage III or stage IV disease, and who were HLA-A*0201-positive, were enrolled in a three-arm, multinational, randomized (3:1:1), double-blind, double-placebo trial. A total of 403 patients were randomly assigned to receive ipilimumab (3 mg/kg every 3 weeks for 4 doses) with glycoprotein 100 (gp100) peptide vaccine. One hundred thirty-seven patients received ipilimumab (3 mg/kg every 3 weeks for 4 doses), and 136 patients received the gp100 vaccine. Patients were stratified by baseline metastases and previous receipt or nonreceipt of IL-2 therapy. Eighty-two of the patients had metastases to the brain at baseline.[7][Level of evidence A1]

Previously treated patients. A total of 676 patients with previously treated, unresectable stage III or stage IV disease, and who were HLA-A*0201-positive, were enrolled in a three-arm, multinational, randomized (3:1:1), double-blind, double-placebo trial. A total of 403 patients were randomly assigned to receive ipilimumab (3 mg/kg every 3 weeks for 4 doses) with glycoprotein 100 (gp100) peptide vaccine. One hundred thirty-seven patients received ipilimumab (3 mg/kg every 3 weeks for 4 doses), and 136 patients received the gp100 vaccine. Patients were stratified by baseline metastases and previous receipt or nonreceipt of IL-2 therapy. Eighty-two of the patients had metastases to the brain at baseline.[7][Level of evidence A1]

The median OS was 10 months in patients who received ipilimumab alone and 10.1 months in those who received ipilimumab with the gp100 vaccine, compared with 6.4 months for patients who received the vaccine alone (HR of ipilimumab alone vs. gp100 alone, 0.66; P < .003; HR of ipilimumab plus vaccine vs. gp100 alone, 0.68; P < .001).

Previously treated patients. A total of 676 patients with previously treated, unresectable stage III or stage IV disease, and who were HLA-A*0201-positive, were enrolled in a three-arm, multinational, randomized (3:1:1), double-blind, double-placebo trial. A total of 403 patients were randomly assigned to receive ipilimumab (3 mg/kg every 3 weeks for 4 doses) with glycoprotein 100 (gp100) peptide vaccine. One hundred thirty-seven patients received ipilimumab (3 mg/kg every 3 weeks for 4 doses), and 136 patients received the gp100 vaccine. Patients were stratified by baseline metastases and previous receipt or nonreceipt of IL-2 therapy. Eighty-two of the patients had metastases to the brain at baseline.[7][Level of evidence A1]

An analysis at 1 year showed that 44% of patients who were treated with ipilimumab and 45% of those treated with ipilimumab and the vaccine were alive, compared with 25% of the patients who received the vaccine only.

Previously treated patients. A total of 676 patients with previously treated, unresectable stage III or stage IV disease, and who were HLA-A*0201-positive, were enrolled in a three-arm, multinational, randomized (3:1:1), double-blind, double-placebo trial. A total of 403 patients were randomly assigned to receive ipilimumab (3 mg/kg every 3 weeks for 4 doses) with glycoprotein 100 (gp100) peptide vaccine. One hundred thirty-seven patients received ipilimumab (3 mg/kg every 3 weeks for 4 doses), and 136 patients received the gp100 vaccine. Patients were stratified by baseline metastases and previous receipt or nonreceipt of IL-2 therapy. Eighty-two of the patients had metastases to the brain at baseline.[7][Level of evidence A1]

Grade 3 or grade 4 irAEs occurred in 10% to 15% of patients treated with ipilimumab. These irAEs most often included diarrhea or colitis, and endocrine-related events (e.g., inflammation of the pituitary). These events required cessation of therapy and institution of anti-inflammatory agents such as corticosteroids or, in four cases, infliximab (an antitumor necrosis factor-alpha antibody).

Previously treated patients. A total of 676 patients with previously treated, unresectable stage III or stage IV disease, and who were HLA-A*0201-positive, were enrolled in a three-arm, multinational, randomized (3:1:1), double-blind, double-placebo trial. A total of 403 patients were randomly assigned to receive ipilimumab (3 mg/kg every 3 weeks for 4 doses) with glycoprotein 100 (gp100) peptide vaccine. One hundred thirty-seven patients received ipilimumab (3 mg/kg every 3 weeks for 4 doses), and 136 patients received the gp100 vaccine. Patients were stratified by baseline metastases and previous receipt or nonreceipt of IL-2 therapy. Eighty-two of the patients had metastases to the brain at baseline.[7][Level of evidence A1]

There were 14 drug-related deaths (2.1%), and seven deaths were associated with irAEs.

Previously untreated patients. A multicenter, international trial included 502 patients who were untreated for metastatic disease (adjuvant treatment was allowed). Patients were randomly assigned (1:1) to receive either ipilimumab (10 mg/kg) plus dacarbazine (850 mg/m2) or placebo plus dacarbazine (850 mg/m2) at weeks 1, 4, 7, and 10 followed by dacarbazine alone every 3 weeks through week 22. Patients with stable disease or an objective response and no dose-limiting toxic effects received ipilimumab or placebo every 12 weeks thereafter as maintenance therapy. The primary end point was survival. Patients were stratified according to ECOG PS and metastatic stage. Approximately 70% of the patients had an ECOG PS of 0, and the remainder of the patients had an ECOG PS of 1. Approximately 55% of patients had stage M1c disease.[6][Level of evidence A1]

Previously untreated patients. A multicenter, international trial included 502 patients who were untreated for metastatic disease (adjuvant treatment was allowed). Patients were randomly assigned (1:1) to receive either ipilimumab (10 mg/kg) plus dacarbazine (850 mg/m2) or placebo plus dacarbazine (850 mg/m2) at weeks 1, 4, 7, and 10 followed by dacarbazine alone every 3 weeks through week 22. Patients with stable disease or an objective response and no dose-limiting toxic effects received ipilimumab or placebo every 12 weeks thereafter as maintenance therapy. The primary end point was survival. Patients were stratified according to ECOG PS and metastatic stage. Approximately 70% of the patients had an ECOG PS of 0, and the remainder of the patients had an ECOG PS of 1. Approximately 55% of patients had stage M1c disease.[6][Level of evidence A1]

The median OS was 11.2 months (95% CI, 9.4–13.6) in the ipilimumab-dacarbazine group versus 9.1 months (95% CI, 7.8–10.5) in the placebo-dacarbazine group. In the ipilimumab-dacarbazine group, estimated survival rates were 47.3% at 1 year, 28.5% at 2 years, and 20.8% at 3 years (HRdeath, 0.72; P < .001). In the placebo-dacarbazine group, the survival rates were 36.3% at 1 year, 17.9% at 2 years, and 12.2% at 3 years.

Previously untreated patients. A multicenter, international trial included 502 patients who were untreated for metastatic disease (adjuvant treatment was allowed). Patients were randomly assigned (1:1) to receive either ipilimumab (10 mg/kg) plus dacarbazine (850 mg/m2) or placebo plus dacarbazine (850 mg/m2) at weeks 1, 4, 7, and 10 followed by dacarbazine alone every 3 weeks through week 22. Patients with stable disease or an objective response and no dose-limiting toxic effects received ipilimumab or placebo every 12 weeks thereafter as maintenance therapy. The primary end point was survival. Patients were stratified according to ECOG PS and metastatic stage. Approximately 70% of the patients had an ECOG PS of 0, and the remainder of the patients had an ECOG PS of 1. Approximately 55% of patients had stage M1c disease.[6][Level of evidence A1]

The most common study-drug–related adverse events were those classified as immune related. Grade 3 or grade 4 irAEs were seen in 38.1% of patients treated with ipilimumab plus dacarbazine versus 4.4% of patients treated with placebo plus dacarbazine. The most common events were hepatitis and enterocolitis.

Previously untreated patients. A multicenter, international trial included 502 patients who were untreated for metastatic disease (adjuvant treatment was allowed). Patients were randomly assigned (1:1) to receive either ipilimumab (10 mg/kg) plus dacarbazine (850 mg/m2) or placebo plus dacarbazine (850 mg/m2) at weeks 1, 4, 7, and 10 followed by dacarbazine alone every 3 weeks through week 22. Patients with stable disease or an objective response and no dose-limiting toxic effects received ipilimumab or placebo every 12 weeks thereafter as maintenance therapy. The primary end point was survival. Patients were stratified according to ECOG PS and metastatic stage. Approximately 70% of the patients had an ECOG PS of 0, and the remainder of the patients had an ECOG PS of 1. Approximately 55% of patients had stage M1c disease.[6][Level of evidence A1]

No drug-related deaths occurred.