NCCN Guideline Advises Routine Molecular Testing for Stages III/IV Melanoma

NCCN Guideline Advises Routine Molecular Testing for Stages III/IV Melanoma

Publication date: Apr 15, 2019

The new guideline recommends early BRAF mutation testing in patients with resected stage III melanoma who are considered -high risk” and might be candidates for BRAF-targeted therapy.

For patients who lack actionable BRAF mutations (i. e., BRAF V600E/K), the guideline recommends the use of larger next-generation sequencing (NGS) panels to identify other potentially-targetable genetic alterations, such as mutations in KIT.

Adjuvant immunotherapy is also recommended for this patient population, following clinical trials that suggest benefit from anti-CTLA-4 or anti-PD-1 therapy. The updated guideline highlights the progress that has been made in treating melanoma patients at high risk of disease recurrence and death following surgery.

The NCCN now recommends testing for BRAF mutations in patients with stage III melanoma who are at high risk for recurrence for whom future BRAF-directed therapy may be an option.

For patients with stage IV disease at initial presentation or clinical recurrence, the updated guideline recommends obtaining tissue to ascertain alterations in BRAF, and in the appropriate clinical setting, KIT from either biopsy of the metastasis (preferred) or archival material if the patient is being considered for targeted therapy.

Because BRAF and KIT mutations appear to be early genetic driver events in melanoma, repeat molecular testing upon recurrence or metastases “is likely to be of low yield. “

Patients with stage III/IV melanoma are at higher risk of disease recurrence following resection.

For patients with clinical stage III (clinical or microscopic satellite/in-transit metastases) or resectable stage IV melanoma, adjuvant systemic therapy is an option for patients rendered disease-free by resection.

The randomized COMBI-AD study compared the combination of dabrafenib and trametinib with two matched placebos in patients with stages IIIA, IIIB, or IIIC fully resected melanoma with a BRAF V600E/K mutation who were free of disease ≤12 weeks prior to randomization.

Adjuvant ipilimumab (10 mg/kg every 3 weeks for four doses and then every 3 months) reduced the risk of death by 28% compared with placebo (HR 0. 72, 95% CI 0. 58-0. 88, P=0. 001) in patients with fully resected stage III melanoma in the EORTC 18701 study.

Concepts Keywords
Adjuvant Nivolumab
Adjuvant Therapy Ipilimumab
Benign Adjuvant therapy
Biopsy Targeted therapy
BRAF Trametinib
BRAF Inhibitor Dabrafenib
Clinical Trial Melanoma
Clinical Trials Cancer treatments
Evolution Clinical medicine
Fox Chase Cancer
Gene Adjuvant therapy
Genetic Immunotherapy
Immune Function Surgery
Immunohistochemistry Placebos
Immunotherapies Rationale immunotherapy melanoma
Immunotherapy Management cutaneous melanoma
Inadequate Immunotherapies
Ipilimumab Approximately half melanomas
KIT IV Melanoma
MAP Kinase Guideline melanoma
MEK Annual conference Melanoma
Melanoma IV disease
Melanomas III melanoma
Metastases Guideline management
Metastasis Nevi
Metastatic Clinical microscopic satellite
Mitotic Surgical management
Monotherapy Metastatic disease
Mortality Tumor
Mutant
Mutation
NCCN
Nevi
Oncology
Philadelphia
Placebo
Primary Tumor
Randomization
Relapse
Resection
Satellite
Sequencing
Surgical Resection
Systemic Therapy
Targeted Therapy
Transit
Tumor
Ulceration

Semantics

Type Source Name
gene UNIPROT ARMC9
gene UNIPROT AKR1A1
drug DRUGBANK Nivolumab
gene UNIPROT ALG3
gene UNIPROT NR4A2
drug DRUGBANK Ipilimumab
gene UNIPROT CD274
gene UNIPROT SGSM3
gene UNIPROT MAGEE1
disease MESH nevi
disease MESH metastasis
pathway BSID Gene Expression
gene UNIPROT PDCD1
disease MESH death
disease MESH Melanoma
disease DOID Melanoma
pathway BSID Melanoma
disease MESH Cancer
disease DOID Cancer
disease DOID cutaneous melanoma
disease MESH recurrence
gene UNIPROT BRAF
gene UNIPROT KIT
gene UNIPROT MAP2K7
gene UNIPROT TNFSF14
drug DRUGBANK Dabrafenib
drug DRUGBANK Trametinib
gene UNIPROT CTLA4
gene UNIPROT RPL17

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