BRAF-MEK Inhibitors as Steroid-Sparing Bridge Prior to Checkpoint Blockade Therapy in Symptomatic Intracranial Melanoma

Abstract

The introduction of immune checkpoint blockade (ICB) and BRAF-MEK inhibitors has substantially improved outcomes in patients with metastatic melanoma. However, several challenging factors may hinder the efficacy of ICB in patients with symptomatic intracranial metastatic melanoma who are immunosuppressed due to the use of steroids prior to the administration of ICB. This has resulted in the exclusion of patients treated with high dose steroid at baseline from the majority of ICB clinical trials. In addition, despite the high efficacy of BRAF-MEK inhibitors in BRAF-mutant intracranial metastatic melanoma, most tumors will eventually progress. This demonstrates a gap in addressing the best management in such patients. Here, we present a case demonstrating our approach in this patient population.

Symptomatic brain metastases in melanoma

“…73 There is limited data surrounding the use of a BRAF-MEK inhibitor 'induction' period as a bridge to ICI and to reduce corticosteroid use. 74,75 The SECOMBIT study assessed this approach in extracranial disease, noting high response rates and clinical benefit with 'sandwiched' short course targeted therapy and a planned switch to ICI, followed by targeted therapy again at progression. 76 The TRICOTEL phase II study looked at adding atezolizumab after 28 days of vemurafenib and cobimetinib in BRAF V600 mutated melanoma, and atezolizumab and cobimetinib in BRAF wild-type melanoma, and included over a third of patients with symptomatic MBM.…”

“…There is limited data surrounding the use of a BRAF‐MEK inhibitor ‘induction’ period as a bridge to ICI and to reduce corticosteroid use 74,75 . The SECOMBIT study assessed this approach in extracranial disease, noting high response rates and clinical benefit with ‘sandwiched’ short course targeted therapy and a planned switch to ICI, followed by targeted therapy again at progression 76 .…”