Neoadjuvant Systemic Therapy May Shrink Uveal Melanoma Tumors

When faced with enucleation of a patient’s single viable eye due to a uveal melanoma which was too large for plaque radiation therapy, doctors opted to try systemic darovasertib and crizotinib instead, which resulted in significant reduction in the size of the tumor and preservation of the patient’s eye and vision. Though this was a single case study, and the use of this medication is not FDA approved, the promising outcome suggests that future research into neoadjuvant therapy as a potential treatment option for uveal melanoma may be warranted.

Study Design

Protein kinase C (PKC) and mesenchymal-epithelial transition factor are involved in pathways associated with cell growth. This case report describes the first-ever treatment of a large primary uveal melanoma in a 70-year-old patient using a combination of neoadjuvant darovasertib (PKC inhibitor) and crizotinib (mesenchymal-epithelial transition factor inhibitor) to reduce tumor size as an alternative to enucleation, the only other treatment option with curative potential. The patient was given oral darovasertib 300 mg twice daily for 1 week, after which crizotinib 200 mg was added twice daily for a total of 6 months of treatment

Outcomes

By 6 months, the uveal melanoma tumor thickness decreased by 84%, enabling subsequent treatment with ruthenium plaque brachytherapy. Visual acuity 3 months following plaque brachytherapy and cataract extraction was 6/9 (20/30). During treatment, the patient experienced grade 1 side effects (e.g., diarrhea, acneiform rash, nausea).

Limitations

This is a case report, limiting the ability to draw more global conclusions regarding the treatment’s effectiveness and safety profile. Darovasertib is still under clinical trials for the treatment of metastatic uveal melanoma and for the treatment of primary uveal melanoma as a neoadjuvant, making its availability limited in many centers.

Clinical Significance

This trial presents a possible new treatment option for primary uveal melanoma, especially for patients suffering from large or recurrent melanomas, which are less suitable for primary plaque brachytherapy. With further investigation, neoadjuvant therapy may prove to be a viable method of minimizing tumor size in a disease with minimal therapeutic options.

Financial Disclosures: Dr. Maya Eiger-Moscovich discloses no financial relationships.