Background
Phase III RCT of 287 patients with resected stage IIB or IIIA (T4 and/or node-positive) melanoma, enrolled 1984-1990. Landmark trial of adjuvant high-dose interferon alfa-2b.
Interventions and follow up
Arm A: High-dose IFN alfa-2b (HDI) 20 MU/m2 IV 5d/wk x1mo (induction) then 10 MU/m2 SC 3d/wk x48wk (maintenance)
Arm B: Observation
Primary endpoints: relapse-free survival (RFS) and overall survival (OS)
Median follow-up: 6.9yr
Arm B: Observation
Primary endpoints: relapse-free survival (RFS) and overall survival (OS)
Median follow-up: 6.9yr
Results
Median RFS: 1.72yr vs 0.98yr (HDI vs observation)
5-yr RFS: 37% vs 26%, P=.0023
Median OS: 3.82yr vs 2.78yr
5-yr OS: 46% vs 37%, P=.0237
5-yr RFS: 37% vs 26%, P=.0023
Median OS: 3.82yr vs 2.78yr
5-yr OS: 46% vs 37%, P=.0237
Adverse events
Grade 3 toxicity: occurred in 67% of HDI patients
Severe/life-threatening: grade 4 in 9%; predominant toxicities were hepatotoxicity, myelosuppression, and neurologic/constitutional effects in the majority of HDI patients
Severe/life-threatening: grade 4 in 9%; predominant toxicities were hepatotoxicity, myelosuppression, and neurologic/constitutional effects in the majority of HDI patients
Conclusions
High-dose interferon improved both RFS and OS over observation, becoming the first adjuvant therapy to alter the natural history of high-risk resected melanoma, albeit at the cost of substantial toxicity.
Key Limitations
Small sample size; high-grade toxicity limiting tolerability; older AJCC staging; OS benefit attenuated in later pooled analyses; entirely superseded by modern anti-PD-1 and BRAF/MEK adjuvant therapy.
Clinical Context
Led to FDA approval of high-dose interferon alfa-2b for adjuvant melanoma (1995), the historical standard for nearly two decades. Now obsolete; ESMO no longer recommends adjuvant interferon, favoring anti-PD-1 and targeted therapy.