Systemic Treatments for Unresectable and Metastatic Cutaneous Melanoma

Guideline Objective

The objective of this guideline is to provide guidance on the use of systemic therapy in patients with unresectable, metastatic cutaneous melanomas.

Patient Population

These recommendations apply to adult patients (18+) with unresectable lymph node metastasis (American Joint Committee on Cancer [AJCC] TNM stage IIIC/D) and distant metastatic (AJCC TNM stage IV) cutaneous melanoma for whom systemic therapy is indicated. Pathological staging is according to the 8th edition AJCC staging system.

Intended Guideline Users

The intended users of the guideline are medical oncologists, dermatologists, family doctors and other clinicians who are involved in the treatment and follow-up care of patients with melanoma in the province of Ontario.

Research Questions

Research Question 1

For adult patients (18+) with unresectable lymph node metastasis (AJCC TNM stage IIIC/D) and distant metastatic (AJCC TNM stage IV) cutaneous melanoma:

1. What systemic treatment options (immunotherapies and targeted therapies) with what optimal timing and sequencing, alone or in combination, have demonstrated clinical benefit, compared with traditionally used treatments (chemotherapies, alternative immunotherapies and targeted therapies)?
2. Are there groups of patients with molecular (e.g., BRAF-mutated, NRAS-mutated, KIT-mutated) and/or clinical disease subtypes (e.g., lymph node metastasis, brain metastases) who benefit from certain systemic treatments alone or in combination?

Research Question 2

What is the optimal systemic therapy management of disease progression following treatment breaks in the target population?