Retrospective review of outcomes associated with metastatic melanoma patients treated with 1st‐line BRAF‐targeted therapy

Abstract

BRAF gene driver mutations are found in 40%-50% of patients with metastatic melanoma, and oral kinase inhibitors targeting the MAP kinase pathway have been routinely available in clinical practice for almost a decade (Carlino et al., 2015;Kong et al., 2016). Patients with advanced BRAF-mutant melanoma generally have access to two different treatment modalities: immunotherapy (with immune checkpoint inhibitors) and BRAF-targeted therapies. Understanding how best to sequence these different treatment modalities is a key research priority (Giunta et al., 2020;Pavlick et al., 2019).The apparent advantages of MAP kinase pathway inhibition over immunotherapy include a very high initial response rate which can be achieved within a few weeks of starting treatment,

Multistep tumor genetic evolution and changes in immunogenicity trigger immune-mediated disease eradication in stage IV melanoma: lessons from a single case

“… 13 14 In addition, retrospective analysis of clinical results from a real-world setting revealed that a very low proportion of patients progressing on targeted therapy went on to receive a second-line ICI due to rapid disease progression. 15 Although the current practice does not include the single treatments given to this patient, nonetheless this case indicates that immunotherapy rechallenge after targeted therapy in combination with surgical debulking can be effective, and that acquired resistance to ICIs in melanoma can be reversed, with resistant tumors potentially showing a response to therapy rechallenge. 16 17 Even though it is not clear how commonly this change may occur, this particular case clearly shows that kinase inhibitors strongly regulated the TIME and tumor evolution from an immunologically cold to a hot tumor, thereby augmenting the effectiveness of immunotherapy, as previously shown for targeted therapy and for some other types of therapy.…”