| General information |
| Database: | DB00201 |
| Objective: | An improvement in overall survival among patients with metastatic melanoma has been an elusive goal. In thisphase 3 study, ipilimumabwhich blocks cytotoxic Tlymphocyteassociated antigen 4 to potentiate an antitumor Tcell responseadministered with or without a glycoprotein 100 (gp100) peptide vaccine was compared with gp100 alone in patients with previously treated metastatic melanoma. |
| Authors: | Hodi FS, et al |
| Title: | Improved survival with ipilimumab in patients with metastatic melanoma. |
| Journal: | N Engl J Med. |
| Year: | 2010 |
| PMID: | 20525992 |
| Trial Design |
| Clinical Trial Id: | NCT00094653 |
| Agent: | ipilimumab
|
| Target: | Cytotoxic Tlymphocyte antigen 4 (CTLA4)
|
| Cancer Type: | melanoma |
| Cancer Subtype: | advanced melanoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a randomized, doubleblind, phase III study |
| Key Patients Feature: | HLAA*0201positive patients with unresectable stage III or IV melanoma, whose disease had progressed while were receiving therapy for metastatic disease, |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | administered with or without a glycoprotein 100 (gp100) peptide vaccine was compared with gp100 alone |
| Treatment Info: | pts were randomly assigned, in a 3:1:1 ratio, to receive ipilimumab plus gp100 (403 patients), ipilimumab alone (137), or gp100 alone (136). Ipilimumab, at a dose of 3 mg per kilogram of body weight, was administered with or without gp100 every 3 weeks for up to four treatments (induction). |
| Primary End Point: | the best overall response rate. The primary comparison in overall survival was between the ipilimumabplusgp100 group and the gp100alone group. |
| Secondary End Point: | a comparison of overall survival between the ipilimumabalone and the gp100alone groups and between the two ipilimumab groups, the best overall response rate, the duration of response, and progression free survival. |
| Patients Number: | 676 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | The median OS was 10.0 months among patients receiving ipilimumab plus gp100, as compared with 6.4 months among pts receiving gp100 alone (HR for death, 0.68; P<0.001). The median overall survival with ipilimumab alone was 10.1 months (HR for death in the comparison with gp100 alone, 0.66; P=0.003). No difference in overall survival was detected between the ipilimumab groups (HR with ipilimumab plus gp100, 1.04; P=0.76). |
| Adverse Event(agent arm): | Grade 3 or 4 immunerelated adverse events occurred in 10 to 15% of patients treated with ipilimumab and in 3% treated with gp100 alone. There were 14 deaths related to the study drugs (2.1%), and 7 were associated with immunerelated adverse events. |
| Conclusions: | Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma. Adverse events can be severe, longlasting, or both, but most are reversible with appropriate treatment. |