Pembrolizumab for the adjuvant treatment of IIB or IIC melanoma

ABSTRACT

Introduction

Up to 30% of patients with stage IIB and 50% of stage IIC melanoma experience recurrence within 5 years after radical surgery. Adjuvant treatment is expected to improve this prognosis.

Areas covered

Pembrolizumab (MK-3475) is a humanized monoclonal antibody that acts against the programmed cell death 1 (PD-1) receptor. Pembrolizumab was first approved in monotherapy for the treatment of unresectable/metastatic melanoma based on the results of the prospective KEYNOTE-001, KEYNOTE-002, and KEYNOTE-006 trials. KEYNOTE-716 is the randomized phase III trial of pembrolizumab treatment in resected stage II melanoma. Treatment with pembrolizumab is statistically significant, reducing the risk of recurrence as well as distant metastases risk after primary tumor resection. Pembrolizumab treatment has a 24-month RFS rate of 81.2% (HR 0.64 vs placebo) and a DMFS rate of 88.1%.

Expert opinion

1-year adjuvant pembrolizumab treatment of stage IIB/C melanoma patients significantly reduces recurrence or death risk. The safety profile of adjuvant treatment is not different from previously reported and is manageable. Longer follow-up is required to fully understand the efficacy and safety of adjuvant therapy for stage II melanoma, as the number of patients needed to treat is twice as high as for stage III patients.

KEYWORDS:

• Adjuvant treatment
• anti-PD-1
• immunotherapy
• melanoma
• PD-1
• pembrolizumab

Article highlights

• Patients with stage IIB and IIC melanoma, especially those with ulcerated primary tumor, are at the same risk of disease recurrence and/or melanoma-related death as those with stage IIIA and IIIB disease.

• For stage IIB melanoma, half of all recurrences are expected within 2 years from the diagnosis of the primary tumor.

• For stage IIC melanoma, more than 50% of patients have distant metastasis as their first recurrence.

• KEYNOTE-716 is the randomized phase III trial of systemic anti-PD-1 (pembrolizumab) treatment in resected stage II resected melanoma.

• Treatment with pembrolizumab statistically significantly reduced recurrence risk in stage II melanoma after primary tumor resection.

• Adjuvant pembrolizumab significantly improves DMFS in stage IIB and IIC melanoma.

• Adjuvant immunotherapy for patients with high-risk stage II melanoma may be recommended for selected patients, but established predictive factors may be necessary for the proper selection of patients who benefit the most.

Declaration of interest

P Rutkowski has received fees for lectures and participation in Advisory Boards from Novartis, Bristol Myers Squibb, Merck Sharp & Dohme, Pierre Fabre, Merck, Sanofi, Amgen, Blueprint Medicines. A Czarnecka has received fees for lectures and clinical trials from Bristol Myers Squibb, Merck Sharp & Dohme, Roche.

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 paper received no funding.