EORTC 18071
Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma
Phase 3N = 951NCT00636168
- Population
- Patients with completely resected stage III cutaneous melanoma (excluding lymph node metastasis of 1 mm or less or in-transit metastasis) who had not received previous systemic therapy for melanoma
- Design
- Double-blind, randomised (1:1), placebo-controlled phase 3 trial. Ipilimumab 10 mg/kg or placebo every 3 weeks for four doses, then every 3 months for up to 3 years. Randomisation stratified by disease stage and geographical region. Primary endpoint recurrence-free survival assessed by an independent review committee, analysed by intention to treat; secondary endpoints included overall survival and distant metastasis-free survival.
- Primary endpoint
- RFS
- Arms
- Ipilimumab 10 mg/kg (experimental, n = 475): Ipilimumab 10 mg/kg every 3 weeks for four doses, then every 3 months for up to 3 years
- Placebo (control, n = 476): Placebo on the same schedule
- People
- Eggermont AM, senior author Testori A, EORTC
RFSHR 0.75 (95% CI 0.64–0.90)Δ median RFS+9 monthsΔ 36-month RFS+11.7 pointsOSHR 0.72Δ 60-month OS+11 pointsRFSHR 0.76 (95% CI 0.64–0.89)
Show the numbers
| Endpoint | Analysis | Ipilimumab 10 mg/kg | Placebo | Effect |
|---|---|---|---|---|
| RFS | primarymedian follow-up 2.74 yearsEggermont 2015 | median 26.1 months (19.3–39.3); 46.5% at 3 y (41.5–51.3%) | median 17.1 months (13.4–21.6); 34.8% at 3 y (30.1–39.5%) | HR 0.75 (95% CI 0.64–0.90)P=0.0013528 recurrence-free survival events (234 vs 294). Grade 3 to 4 immune-related adverse events were most often gastrointestinal (16% vs under 1%), hepatic (11% vs under 1%) and endocrine (8% vs none). Adverse events led to discontinuation in 245 (52%) of 471 patients who started ipilimumab. Five patients (1%) died of drug-related adverse events. |
| OS | long term-updatemedian follow-up 5.3 yearsEggermont 2016 | 65.4% at 5 y | 54.4% at 5 y | HR 0.72P=0.001Hazard ratio for death 0.72 with a 95.1% confidence interval of 0.58 to 0.88 (not a 95% interval). Secondary endpoint. Grade 3 or 4 adverse events 54.1% vs 26.2%; immune-related grade 3 or 4 41.6% vs 2.7%; 5 patients (1.1%) died of immune-related adverse events. |
| RFS | long term-updatemedian follow-up 5.3 yearsEggermont 2016 | 40.8% at 5 y | 30.3% at 5 y | HR 0.76 (95% CI 0.64–0.89)P<0.001 |
| DMFS | long term-updatemedian follow-up 5.3 yearsEggermont 2016 | 48.3% at 5 y | 38.9% at 5 y | HR 0.76P=0.002Hazard ratio for death or distant metastasis 0.76 with a 95.8% confidence interval of 0.64 to 0.92 (not a 95% interval). Secondary endpoint. |
| Endpoint | Analysis | Ipilimumab 10 mg/kg | Placebo | Effect |
|---|---|---|---|---|
| RFS | primarymedian follow-up 2.74 yearsEggermont 2015 | median 26.1 months (19.3–39.3); 46.5% at 3 y (41.5–51.3%) | median 17.1 months (13.4–21.6); 34.8% at 3 y (30.1–39.5%) | HR 0.75 (95% CI 0.64–0.90)P=0.0013528 recurrence-free survival events (234 vs 294). Grade 3 to 4 immune-related adverse events were most often gastrointestinal (16% vs under 1%), hepatic (11% vs under 1%) and endocrine (8% vs none). Adverse events led to discontinuation in 245 (52%) of 471 patients who started ipilimumab. Five patients (1%) died of drug-related adverse events. |
| OS | long term-updatemedian follow-up 5.3 yearsEggermont 2016 | 65.4% at 5 y | 54.4% at 5 y | HR 0.72P=0.001Hazard ratio for death 0.72 with a 95.1% confidence interval of 0.58 to 0.88 (not a 95% interval). Secondary endpoint. Grade 3 or 4 adverse events 54.1% vs 26.2%; immune-related grade 3 or 4 41.6% vs 2.7%; 5 patients (1.1%) died of immune-related adverse events. |
| RFS | long term-updatemedian follow-up 5.3 yearsEggermont 2016 | 40.8% at 5 y | 30.3% at 5 y | HR 0.76 (95% CI 0.64–0.89)P<0.001 |
| DMFS | long term-updatemedian follow-up 5.3 yearsEggermont 2016 | 48.3% at 5 y | 38.9% at 5 y | HR 0.76P=0.002Hazard ratio for death or distant metastasis 0.76 with a 95.8% confidence interval of 0.64 to 0.92 (not a 95% interval). Secondary endpoint. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| RFS | 0.75 | 0.64–0.9 |
| RFS | 0.76 | 0.64–0.89 |
- Ipilimumab 10 mg/kg (experimental)
- Placebo (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Ipilimumab 10 mg/kg | Placebo |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 16 | 65.4% | 52.3% |
| 33 | 41.6% | 26.2% |
| 49 | 27.2% | 13.7% |
| 65 | 17.8% | 7.2% |
Appears in
Sources
Eggermont AM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, et al. Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2015;16(5):522-30.
Eggermont AM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, et al. Prolonged Survival in Stage III Melanoma with Ipilimumab Adjuvant Therapy. N Engl J Med. 2016;375(19):1845-1855.