Overview of the management of advanced cutaneous melanoma
- Jeffrey A Sosman, MD
Jeffrey A Sosman, MD
- Professor of Medicine
- Robert H. Lurie Comprehensive Cancer Center of Northwestern
Most cases of malignant melanoma are diagnosed at an early stage, when surgical excision can be curative. However, a few patients have metastatic disease at presentation, and some develop metastases after their initial definitive treatment.
High-dose interleukin-2 (IL-2) was the first treatment to modify the natural history of patients with metastatic melanoma and may have resulted in cure in a small fraction of patients. However, its severe toxicity limited its application to carefully selected patients treated at centers with experience in managing the side effects of treatment.
More recent research led to the development of immunotherapy using checkpoint inhibitors (the anti-programmed cell death 1 [PD-1] antibodies [pembrolizumab, nivolumab] and the anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA-4] antibody [ipilimumab]) and targeted therapy (inhibition of the BRAF and/or MEK genes). Both checkpoint inhibitor immunotherapy and targeted therapy prolong progression-free and overall survival compared with chemotherapy, which has not been proven to increase overall survival.
This topic provides an overview of treatment options for patients with metastatic melanoma, along with their applications in different clinical settings. More detailed discussions of each of the specific treatment options are presented separately:
- Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med 2015; 373:23.
- Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011; 364:2507.
- Schreuer M, Jansen Y, Planken S, et al. Combination of dabrafenib plus trametinib for BRAF and MEK inhibitor pretreated patients with advanced BRAF(V600)-mutant melanoma: an open-label, single arm, dual-centre, phase 2 clinical trial. Lancet Oncol 2017; 18:464.
- Ackerman A, Klein O, McDermott DF, et al. Outcomes of patients with metastatic melanoma treated with immunotherapy prior to or after BRAF inhibitors. Cancer 2014; 120:1695.
- TREATMENT OPTIONS
- Surgical metastasectomy
- Targeted therapy
- - MAP kinase pathway inhibition
- - KIT mutations
- Radiation therapy
- Cytotoxic chemotherapy
- INITIAL EVALUATION
- CHOICE AND SEQUENCE OF THERAPY
- Therapeutic approach
- - Oligometastatic disease
- - No driver mutation
- - Driver mutation present
- Brain metastases
- Locoregional therapy
- FOLLOW-UP DURING AND AFTER TREATMENT
- SUMMARY AND RECOMMENDATIONS