[New systemic treatment approaches for conjunctival melanoma]

Conjunctival melanoma is a rare disease that nevertheless has a high tumor-associated mortality rate. A resection in sano with adjuvant local treatment currently represents the therapeutic gold standard and systemic treatment is used for metastasized conjunctival melanoma and/or very advanced nonresectable local findings. New knowledge on molecular changes in conjunctival melanoma shows a clear similarity to those of cutaneous melanoma. Therefore, many findings on new systemic forms of treatment for cutaneous melanoma can be transferred to conjunctival melanoma. In the clinical application BRAF/MEK inhibitors and immune checkpoint inhibitors are already in use and good response rates have been shown in small retrospective studies and case reports. Due to the rarity of conjunctival melanoma, there are no larger prospective studies comparing different systemic therapeutic agents. In a nonrandomized retrospective comparison, a better overall survival was shown for a combination of BRAF/MEK inhibitors (progression-free 1‑year survival probability of 54.7%; overall survival of 29.1 months) compared to a combination of PD1/CTLA4 antibodies (progression-free 1‑year survival probability of 42%; overall survival of 18 months). The current recommendation is to perform genomic profiling for every conjunctival melanoma, particularly to investigate a BRAF mutation. If a BRAF mutation is present, BRAF/MEK inhibitor treatment should preferably be initiated. Treatment with immune checkpoint inhibitors can be used in the case of BRAF-negative mutation status or treatment failure with BRAF/MEK inhibitors. Monotherapy with the CTLA4 antibody ipilimumab is not recommended due to its inferiority to PD1 antibodies. New knowledge in the genomic profiling of conjunctival melanoma could enable further targeted treatment options in the future.