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.
- Beneficial Effect of Adjuvant Dabrafenib Plus Trametinib on Recurrence-Free Survival in Patients With Resected BRAF-Mutant Stage III Melanoma Seems to be Short-Lived.
- What Is the Role of Dabrafenib Plus Trametinib Adjuvant Therapy in Stage IIIA Melanoma?
- Adjuvant systemic therapy in high-risk melanoma.
- Good News on Adjuvant Therapy for Advanced Cutaneous Melanoma.
- Patient-reported outcomes in patients with resected, high-risk melanoma with BRAF or BRAF mutations treated with adjuvant dabrafenib plus trametinib (COMBI-AD): a randomised, placebo-controlled, phase 3 trial.
- Update on BRAF and MEK inhibition for treatment of melanoma in metastatic, unresectable, and adjuvant settings.
- Dr. Olszanski Discusses Advances in Stage III Melanoma