Dabrafenib–trametinib is recommended for the treatment of patients with BRAFV600E mutations who have progressed after ≥1 prior line of systemic therapy [III, A; ESMO-MCBS v1.1 score: 3; ESCAT score: I-B; FDA approved, not EMA approved].

TAFINLAR is indicated, in combination with trametinib, for...the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with BRAF V600E mutation as detected by an FDA-approved test.

Three of four patients with cholangiocarcinoma, a rare cancer that forms in the bile ducts, had confirmed partial responses.

A 59-year-old-woman presented with abdominal discomfort and jaundice due to biliary obstruction...Rapid progression of the disease and the lack of standard second-line chemotherapy in CCA orientated our therapeutic strategy to targeted agents….BRAF (p.V600E) in 15%, TP53 (p.Q16fs*28) in 22%, PIK3R1 (p.M326I) in 41%, and ATM (p.R337H) in 15% of the tested DNA...Dabrafenib (Tafinlar®, Novartis) 150 mg twice a day and trametinib (Mekinist®, Novartis) 2 mg daily was initiated...Due to the benign nature of the liver mass and the lack of systemic inflammatory signs therapeutic response was regarded as partial response according to RECIST version 1.1 and combined treatment of dabrafenib plus trametinib was continued.

A 71-year-old lady presented with vague right sided abdominal discomfort of 3 to 4 months duration with associated anorexia and weight loss...FNA biopsy was consistent with ICC...Foundation One was performed on her initial diagnostic biopsy and confirmed a BRAF V600E mutation. She was started on dabrafenib 150 mg PO BID and trametinib 2 mg PO QD...Her last scan was done 5 months after initiation of BRAF/MEK inhibitors (April 2016, FIG2d) and confirms a partial response to treatment.

A 38-year-old female patient was operated in National Surgery Institute due to cholangiocellular carcinoma....Next generation sequencing was performed which revealed BRAF V600E mutation in tumor cells. Having taken in account the results of genetic sequencing and the availability of specific inhibitors of this gene, we decided to start our patient on dabrafenib 300 mg pro day + trametinib 2 mg/day....After 7 months full response with complete tumor resolution was achieved. Patient is under thorough control and she is free from tumor according to her latest PET scan on December 2018. To our knowledge this case report is longest remission on dabrafenib + trametinib in CCA patients.

CONTRADICTING EVIDENCE: A 49-year-old female presented with abdominal bloating and increasing discomfort…Post operative histopathological examination revealed a 7.3-cm moderately differentiated ICC...Foundation One comprehensive genomic analysis was performed on her original resection specimen and confirmed a BRAF V600E mutation. She was started on dabrafenib 150 mg PO BID (twice a day) and trametinib 2 mg PO QD (once a day) in May 2015. Follow-up imaging studies confirmed a partial response after 6 weeks of treatment and a complete clinical response after 5 months of treatment...At 9 months of treatment, CT imaging confirmed recurrence of disease in the pericardial node and periportal/portacaval lymph nodes and new right pleural disease. Treatment with dabrafenib and trametinib was discontinued.