| General information |
| Database: | DB00006 |
| Objective: | Ipilimumab is an approved treatment for patients with advanced melanoma. They aimed to assess ipilimumab as adjuvant therapy for patients with completely resected stage III melanoma at high risk of recurrence. |
| Authors: | Eggermont AM, et al |
| Title: | Adjuvant ipilimumab versus placebo after complete resection of highrisk stage III melanoma (EORTC 18071): a randomised, doubleblind, phase 3 trial. |
| Journal: | Lancet Oncol. |
| Year: | 2015 |
| PMID: | 25840693 |
| Trial Design |
| Clinical Trial Id: | NCT00636168 |
| Agent: | ipilimumab
|
| Target: | Cytotoxic Tlymphocyte antigen 4 (CTLA4)
|
| Cancer Type: | melanoma |
| Cancer Subtype: | stage III cutaneous melanoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a doubleblind, phase III trial |
| Key Patients Feature: | patients with stage III cutaneous melanoma (excluding lymph node metastasis less than and equal to 1 mm or intransit metastasis) with adequate resection of lymph nodes (ie, the primary cutaneous melanoma must have been completely excised with adequate surgical margins) who had not received previous systemic therapy for melanoma from 91 hospitals located in 19 countries |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | placebo |
| Treatment Info: | Patients were randomly assigned (1:1), centrally by an interactive voice response system, to receive intravenous infusions of 10 mg/kg ipilimumab or placebo every 3 weeks for four doses, then every 3 months for up to 3 years. |
| Primary End Point: | recurrencefree survival, assessed by an independent review committee, and analysed by intention to treat. |
| Secondary End Point: | Enrollment is complete but the study is ongoing for followup for analysis of secondary endpoints. |
| Patients Number: | 951 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | At a median followup of 2.74 years (IQR 2.283.22), there were 528 recurrencefree survival events (234 in the ipilimumab group vs 294 in the placebo group). Median recurrencefree survival was 26.1 months (95% CI 19.339.3) in the ipilimumab group versus 17.1 months (95% CI 13.421.6) in the placebo group (hazard ratio 0.75; 95% CI 0.640.90; p=0.0013); 3year recurrencefree survival was 46.5% (95% CI 41.551.3) in the ipilimumab group versus 34.8% (30.139.5) in the placebo group. |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most common grade 34 immunerelated adverse events were gastrointestinal (75 [16%] vs four [<1%] in the placebo group), hepatic (50 [11%] vs one [<1%]), and endocrine (40 [8%] vs none). Adverse events led to discontinuation of treatment in 245 (52%) of 471 patients who started ipilimumab (182 [39%] during the initial treatment period of four doses). Five patients (1%) died due to drugrelated adverse events. Five (1%) participants died because of drugrelated adverse events; three patients died because of colitis (two with gastrointestinal perforation), one patient because of myocarditis, and one patient because of multiorgan failure with GuillainBarr¨¦ syndrome. |
| Conclusions: | Adjuvant ipilimumab significantly improved recurrencefree survival for patients with completely resected highrisk stage III melanoma. The adverse event profile was consistent with that observed in advanced melanoma, but at higher incidences in particular for endocrinopathies. The riskbenefit ratio of adjuvant ipilimumab at this dose and schedule requires additional assessment based on distant metastasisfree survival and overall survival endpoints to define its definitive value. |