EORTC 18991
Adjuvant pegylated interferon alfa-2b versus observation in resected stage III melanoma
Phase 3N = 1,256NCT00006249
- Population
- Patients with resected stage III melanoma
- Design
- Randomised phase 3 trial. Pegylated interferon alfa-2b 6 mcg/kg per week for 8 weeks (induction), then 3 mcg/kg per week (maintenance) for an intended 5 years, versus observation. Stratified by microscopic or macroscopic nodal involvement, number of positive nodes, ulceration, tumour thickness, sex and centre. Primary endpoint recurrence-free survival; analyses by intention to treat.
- Primary endpoint
- RFS
- Arms
- Pegylated interferon alfa-2b (experimental, n = 627): 6 mcg/kg per week for 8 weeks, then 3 mcg/kg per week for an intended 5 years
- Observation (control, n = 629): Observation after surgery
- People
- Eggermont AM, senior author Keilholz U, EORTC
RFSHR 0.82 (95% CI 0.71–0.96)Δ 48-month RFS+6.7 pointsRFSHR 0.87 (95% CI 0.76–1.00)Δ 84-month RFS+4.5 points
Show the numbers
| Endpoint | Analysis | Pegylated interferon alfa-2b | Observation | Effect |
|---|---|---|---|---|
| RFS | primarymedian follow-up 3.8 yearsEggermont 2008 | 45.6% at 4 y | 38.9% at 4 y | HR 0.82 (95% CI 0.71–0.96)P=0.014-year rates are given with standard errors (2.2 for each group), not confidence intervals. 328 vs 368 recurrence events. The abstract states there was no difference in overall survival (no value given). Grade 3 adverse events 40% vs 10%; grade 4 5% vs 2%; discontinuation because of toxicity 31% of the interferon group. |
| RFS | long term-updatemedian follow-up 7.6 yearsEggermont 2012 | 39.1% at 7 y | 34.6% at 7 y | HR 0.87 (95% CI 0.76–1.00)P=0.055384 vs 406 recurrences or deaths. No difference in overall survival (P=0.57; no hazard ratio in the abstract). In stage III-N1 ulcerated melanoma (a subgroup analysis; the abstract does not say whether it was prespecified), HR for RFS 0.72 (99% CI 0.46 to 1.13), for DMFS 0.65 (99% CI 0.41 to 1.04), for OS 0.59 (99% CI 0.35 to 0.97; P=0.006). Treatment discontinued for toxicity in 37%. |
| Endpoint | Analysis | Pegylated interferon alfa-2b | Observation | Effect |
|---|---|---|---|---|
| RFS | primarymedian follow-up 3.8 yearsEggermont 2008 | 45.6% at 4 y | 38.9% at 4 y | HR 0.82 (95% CI 0.71–0.96)P=0.014-year rates are given with standard errors (2.2 for each group), not confidence intervals. 328 vs 368 recurrence events. The abstract states there was no difference in overall survival (no value given). Grade 3 adverse events 40% vs 10%; grade 4 5% vs 2%; discontinuation because of toxicity 31% of the interferon group. |
| RFS | long term-updatemedian follow-up 7.6 yearsEggermont 2012 | 39.1% at 7 y | 34.6% at 7 y | HR 0.87 (95% CI 0.76–1.00)P=0.055384 vs 406 recurrences or deaths. No difference in overall survival (P=0.57; no hazard ratio in the abstract). In stage III-N1 ulcerated melanoma (a subgroup analysis; the abstract does not say whether it was prespecified), HR for RFS 0.72 (99% CI 0.46 to 1.13), for DMFS 0.65 (99% CI 0.41 to 1.04), for OS 0.59 (99% CI 0.35 to 0.97; P=0.006). Treatment discontinued for toxicity in 37%. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| RFS | 0.82 | 0.71–0.96 |
| RFS | 0.87 | 0.76–1 |
Appears in
Sources
Eggermont AM, Suciu S, Santinami M, Testori A, Kruit WH, Marsden J, et al. Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial. Lancet. 2008;372(9633):117-126.
Eggermont AM, Suciu S, Testori A, Santinami M, Kruit WH, Marsden J, et al. Long-term results of the randomized phase III trial EORTC 18991 of adjuvant therapy with pegylated interferon alfa-2b versus observation in resected stage III melanoma. J Clin Oncol. 2012;30(31):3810-8.