Long-term treatment with pegylated interferon alfa-2b in stage III melanoma had a significant and sustained impact on relapse-free survival (RFS), according to the results of what is claimed to be the largest adjuvant trial ever conducted in patients with such melanoma.
Results of the phase III study, led by the European Organisation for the Research and Treatment of Cancer (EORTC) and supported by US drug firm Schering-Plough, were presented by lead investigator Dr Alexander Eggermont at the 43rd Annual Meeting of the American Society of Clinical Oncology.
“Advanced-stage melanoma remains difficult to treat and a need still exists to find treatment options,” said Dr Eggermont, head of surgical oncology at Erasmus University Medical Center, Rotterdam, The Netherlands. “These findings demonstrate the benefit of an increased relapse-free survival (RFS) despite no difference in overall survival.”
Median RFS was 34.8 months in the pegylated interferon alfa-2b arm vs 25.5 months in the observational arm (p=0.01). Median distant metastasis-free survival (DMFS) was 45.6 months in subjects receiving pegylated interferon alfa-2b therapy versus 36.1 months in observational arm (p=0.11).
Response to therapy appeared to be most pronounced in a subgroup of subjects with only microscopic nodal involvement – patients with positive sentinel node(s) who experienced both increased relapse-free survival (RFS; p=0.02) and distant metastasis-free survival (DMFS; p=0.03). This group of patients constituted 43% of the trial population. At present, due to the increased use of sentinel-node staging, this patient population constitutes the majority of patients diagnosed with stage III disease.
In the study, participants reached a median 88% and 83% relative dose intensity during the induction and maintenance phases, respectively. Forty percent (251 subjects) ceased pegylated interferon alfa-2b therapy due to toxicity or patient’s withdrawal of consent, while some 23% of subjects continued into year 4 and 5 of treatment.
Grade 3 or 4 toxicities, mostly grade 3 in severity, were reported in 45% of subjects in the pegylated interferon alfa-2b arm vs 12% in the observational arm. These events included primarily Grade 3 fatigue, hepatotoxicity and depression.
An ECOG 0-1 performance status was maintained in 83% of patients during the maintenance phase. These data represent the planned final analysis with a median follow-up of 3.8 years; study participants will be followed for survival for a total of 10 years.
Schering-Plough Corporation press release, 2/6/2007