The efficacy and safety of adjuvant interferon-alfa therapy in the evolving treatment landscape for resected high-risk melanoma

ABSTRACT

Introduction: Patients with resected stage II or III melanoma are at high risk of recurrence, with 5-year mortality rate of 40–60%. Adjuvant interferon-alfa has demonstrated a small RFS and OS benefit versus observation in this patient population. However, the adjuvant treatment landscape is evolving rapidly.

Areas covered: This review aims to summarize the safety and efficacy profiles of adjuvant IFNα/PEG-IFNα, revisit the controversy surrounding its application, and reappraise its position in the rapidly changing treatment landscape of resected melanoma. A literature search using PubMed database was undertaken using search words melanoma, interferon-alfa, pegylated interferon-alfa, adjuvant therapy.

Expert opinion: Currently, there is no international consensus regarding the optimal dosing schedule for adjuvant IFNα, but HD IFNα-2b remains the most widely used regimen. The AEs of HD IFNα-2b are substantial; however, toxicity management experience amassed over the past 2 decades has significantly improved safety. Many exciting studies are ongoing to examine the roles of immune checkpoint inhibitors and BRAF-targeted therapies in the adjuvant setting and will further delineate the role of adjuvant IFNα.

KEYWORDS:

• Melanoma
• interferon-alfa
• pegylated interferon-alfa
• adjuvant therapy

Article highlights

• Adjuvant interferon-alfa (IFNα) has demonstrated small relapse-free and overall survival benefits versus observation in patients with resected stage II or III melanoma.

• There is no international consensus regarding the optimal dosing schedule for adjuvant IFNα; however, high dose regimen at 20 MU/m2 intravenously 5 times per week for 4 weeks followed by 10 MU/m2 subcutaneously three times weekly for 48 weeks is the most commonly used option.

• Adverse events of high-dose IFNα can profoundly affect patients’ quality of life but are manageable with vigilant monitoring, appropriate supportive care, and judicious dose modification

• Many ongoing studies to examine the roles of checkpoint inhibitors and BRAF-targeted therapies in the adjuvant setting will define the role of adjuvant IFNα in the near future.

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Declaration of interest

WJ Hwu has received research grants from Bristol-Myers Squibb, Merck, GlaxoSmithKline, MedImmune and has servered on advisory boards for MedImmune and Merck. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper has not been funded.