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NCCN guideline advises routine moleculat testing for stages 3/4 melanoma.
ASCO released article 4/13/19
Critique by Michael Giles:
This article describes a recent update to the National Comprehensive Cancer Network's (NCCN) guideline for management of cutaneous melanoma. NCCN guidelines are the recognized standard for policy in cancer care and are updated frequently. The updated guideline for melanoma includes recommendations for patients with stage III/IV disease. These individuals are at high risk of recurrence after surgical resection and hence may benefit from molecular testing and adjuvant therapy. 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. The updated guideline also reflects recent advances in targeted therapy or immunotherapy in the adjuvant setting for resected stage III/IV melanoma. Combined BRAF/MEK inhibition is an option that is recommended for BRAF-mutant patients, in light of the COMBI-AD study which showed higher relapse-free survival at 4 years with dabrafenib and trametinib compared with treatment with placebo. 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. It will be interesting to follow the evolution of the use of targeted NGS mutation panels to guide treatment decision-making or future clinical trials, particularly given the paucity of actionable driver mutations beyond BRAF and KIT in the disease. Eventually, this same approach could be applied to the use of immuno-oncology gene expression panels to guide selection of the most appropriate checkpoint inhibitor therapy for a patient, or to prioritize patients for immunotherapy vs targeted therapy (or vice versa). In this regard, several companies are developing immune signatures to predict benefit from checkpoint inhibitor treatment. Future NCCN guidelines for melanoma will need to incorporate a larger number of adjuvant therapy options – in particular, combination immunotherapies - that are likely to become available.
peace and happy research reading,
Missy
