Acute encephalopathy with combination dabrafenib/trametinib therapy

Abstract

Biomarkers have improved the clinical application of numerous targeted agents used to treat solid tumors. In melanoma, the finding that approximately 60% of tumor cells harbor specific Val600 mutations of BRAF has increased the likelihood of response to certain agents aimed at inhibiting the mutant kinase. While dabrafenib is an effective anti-tumor agent with acceptable tolerability in patients with BRAF-mutated melanoma, we report the development (and outcome) of a previously unpublished acute toxic reaction observed in a patient receiving the drug.

Posterior reversible encephalopathy syndrome due to combination of vemurafenib and cobimetinib for metastatic melanoma

“…Posterior reversible encephalopathy syndrome has been previously described 10 days after the first dose of treatment with ipilimumab prescribed for a metastatic melanoma (Maur et al, 2012). An acute encephalopathy has been reported in a patient 1 week after a third-line treatment with dabrafenib and trametinib for metastatic melanoma (Cooper et al, 2016). In this study, only a normal CT scan was performed, and only the reversibility of the symptoms suggested the diagnosis.…”

Posterior reversible encephalopathy syndrome in a melanoma patient with dabrafenib and trametinib treatment following immunotherapy

“…Furthermore, overlap effects after switching treatment from immunotherapy to dabrafenib plus trametinib could be implicated in the occurrence of PRES. One of the previously discussed cases with possible PRES occurred one month after switching a nivolumab treatment directly to dabrafenib plus trametinib without any treatment-free interval [10]. Finally, a late carry-over effect from immunotherapy with ipilimumab plus nivolumab may have been the trigger, as immune-related adverse events may occur even after cessation of immunotherapy [16,17].…”

“…To the best of our knowledge, there are only four case reports on PRES under novel melanoma treatments [8][9][10][11]. However, the diagnosis of PRES in these cases was not completely reliable because an MRI was not performed [8,10].…”

“…To the best of our knowledge, there are only four case reports on PRES under novel melanoma treatments [8][9][10][11]. However, the diagnosis of PRES in these cases was not completely reliable because an MRI was not performed [8,10]. The possibilities that we considered regarding the pathogenesis of PRES in our patient included an adverse event due to therapy with dabrafenib plus trametinib, an overlap effect after the switch from immunotherapy to dabrafenib plus trametinib, and a late carry-over effect from the immunotherapy with ipilimumab plus nivolumab.…”

Posteriores reversibles Enzephalopathie‐Syndrom bei einem Melanompatienten unter Dabrafenib‐ und Trametinib‐Behandlung nach Immuntherapie

“…Nach unserem besten Wissen gibt es nur vier Fallberichte, in denen ein PRES durch eine der neuen Melanomtherapien ausgelöst wurde [8][9][10][11]. Jedoch wurde die Diagnose PRES in all diesen Fällen nicht hinlänglich gesichert, da unter anderem keine MRT durchgeführt wurden [8,10].…”