Briefer Biochemotherapy Yields Better Relapse-Free Survival but Greater Toxicity vs 1-Year High-Dose Interferon in High-Risk Melanoma
In a phase III trial (Southwest Oncology Group Intergroup S0008) reported in the Journal of Clinical Oncology, Flaherty et al found that a shorter course of biochemotherapy consisting of cisplatin, vinblastine, dacarbazine, interleukin-2, and interferon alfa-2b produced better relapse-free survival, but not overall survival, and was associated with greater toxicity compared with a 1-year high-dose interferon alfa-2b regimen in patients with high-risk melanoma. The trial is a Cancer and Leukemia Group B, Children’s Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group Intergroup study.
Study Details
In the trial, 402 patients aged ≥ 10 years with stage IIIA-N2a through IIIC-N3 melanoma were randomly assigned between September 2000 and November 2007 to receive biochemotherapy plus granulocyte colony-stimulating factor given every 21 days for three cycles (n = 199) or high-dose interferon alfa-2b intravenously 5 days per week for 4 weeks and subcutaneously three times per week for 48 weeks (n = 203). The coprimary endpoints were relapse-free survival and overall survival.
The high-dose interferon and biochemotherapy groups were generally balanced for age (median, 48 and 46 years), sex (69% and 71% male), race/ethnicity (96% and 95% white), number of involved nodes (1–3 or satellite/in-transit only in 76% in both), nodal involvement (micrometasteses only in 43% and 44%), and ulceration (41% in both).
Relapse-Free Survival and Overall Survival
Median follow-up was 7.2 years. Median relapse-free survival was 4.0 years (95% confidence interval [CI] = 1.9 years to not reached) in the biochemotherapy group vs 1.9 years (95% CI = 1.2–2.8 years) in the high-dose interferon group (hazard ratio [HR] = 0.75, P = .015), with 5-year relapse-free survival of 48% vs 39%. Median overall survival was 9.9 (95% CI = 4.62 years to not reached) vs 6.7 years (95% CI = 4.5 years to not reached; HR = 0.98, P = .55), with 5-year overall survival of 56% in both groups.
Toxicity
Grade 3 and 4 adverse events occurred in 36% and 40% of biochemotherapy patients and in 57% and 7% of high-dose interferon patients. Grade 4 leukopenia (13% vs 1%), neutropenia (26% vs 4%), and thrombocytopenia (14% vs 0%) were significantly more common in the biochemotherapy group (all P < .01). Among grade 3 or 4 adverse events, anorexia (5% vs 1%), nausea (28% vs 5%), vomiting (20% vs 5%), hypocalcemia (8% vs 0%), and hypotension (9% vs 0%) were more common in the biochemotherapy group, and depression (7% vs 2%), fatigue/lethargy (20% vs 11%), increased AST (9% vs 4%), and increased ALT (16% vs 4%) were more common in the high-dose interferon group (all P ≤ .05). One treatment-related death occurred in each group.
The investigators concluded: “Biochemotherapy is a shorter, alternative adjuvant treatment for patients with high-risk melanoma that provides statistically significant improvement in [relapse-free survival] but no difference in [overall survival] and more toxicity compared with [high-dose interferon].”
Lawrence E. Flaherty, MD, of Karmanos Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by National Cancer Institute grants and by Novartis Pharmaceuticals.
For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
