Safety of pembrolizumab for resected stage III melanoma

ABSTRACT

Introduction

Patients with resected stage III melanoma have a heterogeneous prognosis with an especially high risk of relapse for patients with stage IIIB, IIIC and IIID according to the 2018 classification in AJCC Cancer Staging Manual, 8^th edition (AJCC-8). Ipilimumab was the first immune checkpoint inhibitor (ICI) to show prolonged overall survival (OS) but at the cost of high toxicity. Pembrolizumab and nivolumab are inhibitors of programmed cell death 1 (PD-1) and showed prolonged relapse-free survival (RFS) in patients with resected stage III melanoma at high risk of relapse compared to placebo and ipilimumab, respectively.

Areas covered

The aim of this article is to review the mechanisms of action, pharmacokinetics and safety data of pembrolizumab in resected stage III melanoma and to compare its safety profile to other immune checkpoint inhibitors for the same indication.

Expert opinion

Pembrolizumab as adjuvant therapy of resected stage III melanoma showed an acceptable safety profile, which is comparable to that in advanced melanoma. However, it caused one death. There is uncertainty about its benefits in AJCC-8 stage IIIA melanoma patients. Additionally, caution is required since OS and long-term safety data are not available yet.

KEYWORDS:

• Adjuvant
• anti-PD-1 antibody
• immune checkpoint inhibitors
• melanoma
• pembrolizumab
• safety
• stage III
• toxicity

Declaration of interest

S Dalle is principal investigator in clinical trials promoted by BMS, Novartis, Regeneron, Merck and MSD, he was invited to a congress by MSD and BMS. He received institutional research grants from BMS and MSD. 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they are an employee of Immuneering Corporation. All other peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.