The Role of Systemic Therapy in Melanoma Brain Metastases

A Narrative Review

Kainat Saleem; Diwakar Davar


Chin Clin Oncol. 2022;11(3):24 

In This Article

Future Directions

Multiple studies have been developed to improve upon prior results, and are summarized in Table 4. These include systemic ICIs in combination with agents such as VEGF inhibitors lenvatinib (KEYMAKER-U02D, NCT04700072) and bevacizumab (NCT04356729), novel glutamate modulator troriluzole (NCT04899921), and tumor treating fields (TTF) devices such as NovoTTF-100A (NCT04129515) or Sonocloud (SONIMEL01, NCT04021420).

Beyond the systemic administration of ICIs, IT approaches using various immunotherapies are currently being investigated in melanoma. IT IL-2 was first assessed in patients with melanoma patients with LMD. While response rates were low and the associated toxicities significant, a subset of melanoma patients with LMD treated with IT IL-2 achieved durable long-term survival with 1-, 2- and 5-year OS rates of 36%, 26%, and 13%.[147] An ongoing study (NCT03025256) is evaluating combined systemic and IT nivolumab in this patient population.

As noted earlier, compelling data suggests synergies between PD-1 or CTLA-4 targeting ICIs and RT for the treatment of MBM, supported by data from retrospective series.[148] These have led to a plethora of studies evaluating SRS combined with either single agent anti-PD-1 (NCT02716948, NCT02978404, and NCT02858869) or PD-1/CTLA-4 doublet (NCT03340129) in MBM.

Other studies are evaluating novel small molecules including the class I selective oral HDAC inhibitor HBI-8000 (NCT04674683) and STAT3 inhibitor WP1066 (NCT01904123).