E1609
Adjuvant ipilimumab (3 or 10 mg/kg) versus high-dose interferon alfa-2b for resected high-risk melanoma: North American Intergroup E1609
Phase 3N = 1,670NCT01274338
- Population
- Adults with resected cutaneous melanoma, AJCC 7th edition stage IIIB, IIIC, M1a or M1b
- Design
- Phase 3 trial, central 1:1:1 randomisation, with a two-step hierarchical comparison: ipilimumab 3 mg/kg versus high-dose interferon first, then ipilimumab 10 mg/kg versus high-dose interferon. Coprimary endpoints overall survival and recurrence-free survival. The ipilimumab 3 mg/kg versus interferon comparison used an intention-to-treat analysis of concurrently randomised patients (n=1,051).
- Primary endpoint
- OS, RFS
- Arms
- Ipilimumab 3 mg/kg (experimental, n = 523): Adjuvant ipilimumab 3 mg/kg
- High-dose interferon alfa-2b (control, n = 636): High-dose interferon alfa-2b
- Ipilimumab 10 mg/kg (experimental, n = 511): Adjuvant ipilimumab 10 mg/kg (described in the abstract as the currently approved adjuvant dose)
- People
- Tarhini AA, senior author Kirkwood JM, North American Intergroup
OSHR 0.78RFSHR 0.85
Show the numbers
| Endpoint | Analysis | Ipilimumab 3 mg/kg / Ipilimumab 10 mg/kg | High-dose interferon alfa-2b | Effect |
|---|---|---|---|---|
| OSConcurrently randomised patients, ipilimumab 3 mg/kg vs interferon (n=1,051), intention-to-treat analysis | primaryTarhini 2020 | — | — | HR 0.78P=0.044Hazard ratio for death 0.78 with a 95.6% repeated confidence interval of 0.61 to 0.99 (not a conventional 95% interval). First step of the hierarchical comparison. Grade 3 or higher treatment-related adverse events 37% (ipilimumab 3 mg/kg), 79% (interferon), 58% (ipilimumab 10 mg/kg); adverse events leading to treatment discontinuation 35%, 20% and 54%. After relapse, ipilimumab or ipilimumab plus anti-PD-1 therapy was used significantly more often in the interferon arm than in either ipilimumab arm (P of 0.001 or lower). |
| RFSConcurrently randomised patients, ipilimumab 3 mg/kg vs interferon (n=1,051), intention-to-treat analysis | primaryTarhini 2020 | — | — | HR 0.85P=0.065Hazard ratio for recurrence or death 0.85 with a 99.4% confidence interval of 0.66 to 1.09 (not a 95% interval); not statistically significant. For ipilimumab 10 mg/kg versus interferon (n=989), the abstract states that trends favouring ipilimumab 10 mg/kg did not reach statistical significance and gives no numbers. |
| Endpoint | Analysis | Ipilimumab 3 mg/kg / Ipilimumab 10 mg/kg | High-dose interferon alfa-2b | Effect |
|---|---|---|---|---|
| OSConcurrently randomised patients, ipilimumab 3 mg/kg vs interferon (n=1,051), intention-to-treat analysis | primaryTarhini 2020 | — | — | HR 0.78P=0.044Hazard ratio for death 0.78 with a 95.6% repeated confidence interval of 0.61 to 0.99 (not a conventional 95% interval). First step of the hierarchical comparison. Grade 3 or higher treatment-related adverse events 37% (ipilimumab 3 mg/kg), 79% (interferon), 58% (ipilimumab 10 mg/kg); adverse events leading to treatment discontinuation 35%, 20% and 54%. After relapse, ipilimumab or ipilimumab plus anti-PD-1 therapy was used significantly more often in the interferon arm than in either ipilimumab arm (P of 0.001 or lower). |
| RFSConcurrently randomised patients, ipilimumab 3 mg/kg vs interferon (n=1,051), intention-to-treat analysis | primaryTarhini 2020 | — | — | HR 0.85P=0.065Hazard ratio for recurrence or death 0.85 with a 99.4% confidence interval of 0.66 to 1.09 (not a 95% interval); not statistically significant. For ipilimumab 10 mg/kg versus interferon (n=989), the abstract states that trends favouring ipilimumab 10 mg/kg did not reach statistical significance and gives no numbers. |