(CHICAGO, IL) – Biochemotherapy (BCT) demonstrates greater improvement in relapse-free survival (RFS) compared to high-dose interferon (HDI) in patients with high-risk melanoma, according to a Phase 3 clinical trial presented at the 2012 American Society of Clinical Oncology Annual Meeting.

“BCT is the first and only therapy to demonstrate a statistically significant improvement in RFS compared to HDI in high-risk stage 3 melanoma patients,” said lead author Lawrence E. Flaherty, MD, Medical Oncologist of Detroit Medical Center, Detroit, MI. A one-year course of HDI is the FDA-approved adjuvant therapy for these patients. However, efforts to modify the IFN dose or schedule have not improved treatment efficacy, and IFN is difficult to combine with other agents due to toxicity. Study investigators sought to determine whether a short course of BCT would be more effective than HDI as adjuvant treatment in patients with stage 3 melanoma.

In this intergroup Phase 3 trial, known as S-0008, patients with high-risk melanoma (Stage 3 A-N2a through Stage 3 C N3) were randomized to either HDI or BCT; the latter was comprised of cisplatin, dacarbazine, vinblastine, IL-2, and IFN with G-CSF. Patients were followed until they reached the two co-primary endpoints of RFS and overall survival (OS). Data were analyzed using a one-sided log rank test at P=0.05.

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At a median follow-up of 6.25 years (minimum >4.0 years), median RFS for BCT was 4.31 years vs. 1.9 years for HDI (P=0.02, HR 0.76 [95% CI: 0.58–0.98]). Five-year RFS for BCT and HDI were 47% vs. 39%, respectively. Median OS did not differ between the two arms; for BCT, median OS was not reached vs. 8.42 years for HDI (HR 1.02 [95% CI: 0.76–1.37]; P=0.56). Five-year survival for both arms was 56%.

Two deaths occurred; one patient on HDI died of apnea at home at completion of induction IFN and one on BCT died at home 24 hours after completion of all treatment. Grade 4 toxicities that occurred at significantly greater rates on the BCT arm were leukopenia (13% vs. 1%), neutropenia (26% vs. 4%), and thrombocytopenia (14% vs. 0); all were P<0.01.

Without a significant OS benefit, BCT does not replace IFN as a standard of care, Dr. Flaherty said. However, BCT may be an attractive alternative to IFN for patients with high-risk melanoma because despite greater toxicity, fewer patients on BCT stopped therapy (15% vs. 19%); a larger percentage of patients completed a full course of therapy (80% vs. 43%); treatment duration is shorter (2 months vs. 12 months); and relapse-free survival is longer. In addition, “the BCT regimen can be modified to accommodate new and more active drugs as they enter the melanoma field,” he concluded.