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Published by American Society of Clinical Oncology · GRADE
Systemic treatment for melanoma has changed rapidly since the introduction of ipilimumab in 2011, substantially improving overall and long-term survival. Due to the increasing availability of new therapies, rising melanoma incidence, and treatment costs, rational evidence-based selection of appropriate therapy is essential.
Key Takeaways
Neoadjuvant pembrolizumab added for resectable stage IIIB-IV. Adjuvant nivolumab or pembrolizumab added for stage IIB-C. Adjuvant nivolumab + ipilimumab added for stage IV. Nivolumab + relatlimab added as an option for unresectable/metastatic regardless of BRAF mutation. Nivolumab + ipilimumab preferred over BRAF/MEK inhibitor therapy in first line. T-VEC removed as option for BRAF wild-type progressing on anti-PD-1. Ipilimumab regimens removed for BRAF-mutated disease after progression on other therapies.
Neoadjuvant pembrolizumab (maximum of three courses of 200 mg once every 3 weeks) followed by resection and adjuvant pembrolizumab (maximum of 15 courses of 200 mg once every 3 weeks) should be offered to patients with clinical and resectable stage IIIB-IV cutaneous melanoma.
Patients with clinical and resectable stage IIIB-IV cutaneous melanoma should be offered or referred for enrollment in clinical trials of neoadjuvant therapy where possible.
Adjuvant pembrolizumab or nivolumab should be offered to patients with resected stage IIB or IIC melanoma.
Adjuvant therapy should not be offered to patients with resected stage IIA melanoma outside of enrollment in a clinical trial.
For patients with resected stage IIIA-D disease that is BRAF wild-type, the following adjuvant therapy options should be offered (in no particular order): nivolumab x 52 weeks OR pembrolizumab x 52 weeks. Ipilimumab and high-dose interferon are not recommended for routine use in adjuvant therapy.
For patients with resected stage IIIA-D disease that is BRAF mutant (V600E/K*), the following adjuvant therapy options should be offered (in no particular order): nivolumab x 52 weeks OR pembrolizumab x 52 weeks OR dabrafenib plus trametinib x 52 weeks.
No recommendation can be made for or against adjuvant BRAF/MEK inhibitor therapy in patients with resected stage III/IV melanoma with BRAF mutations other than V600E/K.
Patients with resected stage IV melanoma should be offered adjuvant therapy.
Reasonable options for therapy are nivolumab alone, nivolumab plus ipilimumab followed by nivolumab, pembrolizumab alone, and dabrafenib plus trametinib (in patients with BRAF V600E/K disease).
For patients with BRAF wild-type, unresectable and/or metastatic cutaneous melanoma, the following treatment options should be offered (in no particular order): nivolumab plus ipilimumab followed by nivolumab OR nivolumab plus relatlimab OR nivolumab OR pembrolizumab.
For patients with BRAF mutant (V600) unresectable and/or metastatic cutaneous melanoma, one of the following treatment options should be offered as first-line therapy: nivolumab plus ipilimumab followed by nivolumab OR nivolumab plus relatlimab OR nivolumab OR pembrolizumab OR dabrafenib plus trametinib OR encorafenib plus binimetinib OR vemurafenib plus cobimetinib.
Combination therapy with nivolumab plus ipilimumab is preferred as first-line therapy over BRAF/MEK inhibitor combination therapy.
After progression on anti–PD-1–based therapy, patients with unresectable and/or metastatic BRAF wild-type cutaneous melanoma may be offered ipilimumab or ipilimumab containing regimens. Patients should be offered or referred for enrollment in clinical trials where possible.
After progression on first-line anti–PD-1–based therapy, patients with BRAF mutant (V600) unresectable and/or metastatic cutaneous melanoma may be offered combination BRAF/MEK inhibitor therapy. Similarly, those who have progressed after combination BRAF/MEK inhibitor therapy may be offered anti–PD-1–based therapy.
For patients with injectable (cutaneous or subcutaneous or nodal) unresectable lesions who are not eligible or do not desire the recommended systemic therapies, talimogene laherparepvec may be offered as primary therapy.
HLA-A*02:01-positive patients with metastatic uveal melanoma should be offered tebentafusp.
For all patients with uveal melanoma other than those addressed by recommendation 4.1.1, no recommendation for or against any specific systemic therapy may be made at this time. Patients should be offered or referred for enrollment in clinical trials where possible.
In the absence of further data, the consensus of the Expert Panel is that patients with unresectable and/or metastatic mucosal melanoma may be offered therapy as described in recommendations 3.1 through 3.5. Patients should be offered or referred for enrollment in clinical trials where possible.
No recommendation for or against any specific systemic therapy for patients with any other form of non-cutaneous melanoma may be made at this time. Patients should be offered or referred for enrollment in clinical trials where possible.
Clinical Topic
Melanoma
Objectives
To provide guidance to clinicians regarding the use of systemic therapy for melanoma.
Target Patient Population
Adult patients with melanoma (cutaneous and noncutaneous).
Target Providers
Therapeutic Area
OncologyGuideline Scope
Inclusion Criteria
Special Populations
System: GRADE
Evidence Levels
Recommendation Strength
Monitoring Guidance
Appropriate monitoring for toxicity and disease progression is necessary, especially for longer dosing cycles (e.g., up to 6 weeks) of anti-PD-1 regimens.
Difficulty
advanced
Learning Paths