The pharmacotherapeutic management of nail unit and acral melanomas

ABSTRACT

Introduction

Acral and nail unit melanomas are rare subtypes of melanoma, which have poor prognoses. Current guidelines for optimal treatment are lacking. Recent clinical trials have evaluated new pharmacotherapeutic agents for melanoma treatment, with dramatically improved survival rates; however, studies on acral and nail unit melanomas are limited in comparison to trials on cutaneous melanoma.

Areas covered

This is a comprehensive review of the literature regarding the available treatment options for acral and nail unit melanomas, with consideration of safety and tolerability.

Expert opinion

Programmed cell death protein 1 inhibitors are more efficacious than cytotoxic T lymphocyte-associated antigen-4 blockers in acral and nail unit melanomas, although both are well-tolerated. Tyrosine kinase inhibitors have good clinical activity, however, data on safety is relatively limited. There is minimal data on high dose interferon α-2b and cyclin-dependent kinase 4 and 6 inhibitors, and efficacy and safety must be evaluated in future trials before they can be recommended for use in this patient population. Prospective clinical trials on acral and nail unit melanomas are lacking, and must be performed in large patient populations, with international collaboration likely necessary in order to enroll adequate participants.

KEYWORDS:

• Acral melanoma
• CDK4/6 inhibitor
• checkpoint inhibitors
• CTLA-4 blockade
• high-dose interferon-α-2b
• immunotherapy
• nail unit melanoma
• PD-1 inhibitor
• toxicity
• tyrosine kinase inhibitor

Article highlights

• PD-1 inhibitors pembrolizumab and nivolumab should be considered first-line treatment for acral and nail unit melanoma, and have relatively low toxicity. Toripalimab cannot be similarly recommended.

• The CTLA-4 blocker ipilimumab can be considered after PD-1 inhibitor therapy, or in cases of intolerance or contraindications to anti-PD-1 therapy.

• Tyrosine kinase inhibitors imatinib mesylate and nilotinib may be useful in achieving sustained remissions, but long-term toxicity has not been studied. Sunitinib and dasatinib should not be used for acral and nail unit melanoma.

• High dose interferon α-2b and cyclin-dependent kinase 4 and 6 inhibitors are poorly studied, and we recommend the use of other agents until efficacy and safety is determined.

• BRAF and MEK inhibitors, in theory, can be safely used for acral and nail unit melanoma patients with BRAF and MEK mutations, but data in these populations is currently limited.

• Chemotherapy can be considered in patients with poor prognosis who have failed other treatments, but should not be considered first-line.

• Combination therapies may improve survival rates, as demonstrated in other melanoma subtypes, but studies on acral and nail unit melanoma are limited and should be prioritized in future research.

• There are no standardized treatment regimens for acral melanomas. Therefore, physicians should exercise clinical judgment in determining individual treatment plans, with consideration of tumor type, trials of previous therapies, and safety.

This box summarizes key points contained in the article.

Declaration of interest

SR Lipner has served as a consultant for Ortho-Dermatologics, Verrica, Hoth Therapeutics, the BelleTorus Corporation and Hexima. 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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was not funded.