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Ref Type Journal Article
PMID (33537843)
Authors Butt SU, Mejias A, Morelli C, Torga G, Happe M, Patrikidou A, Arkenau HT
Title BRAF/MEK inhibitors for BRAF V600E-mutant cancers in non-approved setting: a case series.
Journal Cancer chemotherapy and pharmacology
Vol 87
Issue 3
Date 2021 Mar
URL
Abstract Text The management of cancer has been traditionally dependent on the primary tumour type and specific histologic subtypes. Recently, the introduction of molecular profiling tools and its increasing use in clinical practice has facilitated the emergence of novel genomically driven treatment options within the standard of care landscape as well as in the clinical trial setting. One such aberration is mutation in v-Raf murine sarcoma viral oncogene homolog B (BRAF), which results in hyperactivation of RAS-RAF-MEK-ERK signaling in the Mitogen-activated protein kinases (MAPK) pathway. BRAF and Mitogen-activated protein kinase, extracellular signal-regulated kinase kinase (MEK) inhibitors, although being currently approved for melanoma, non-small cell lung cancer (NSCLC) and colon cancer, have reported activity across other various cancers harbouring BRAF aberrations. It has been proposed that combined MEK and BRAF inhibition could overcome the acquired resistance commonly developed among patients receiving BRAF or MEK inhibitors as monotherapy. We report five cases of BRAF V600E (substitution of glutamic acid for valine in codon 600) aberrant refractory metastatic cancers treated with dual BRAF/MEK combination inhibitor therapy leading to an excellent clinical and radiological response and protracted duration of disease control.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF V600E intrahepatic cholangiocarcinoma predicted - sensitive Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, combination treatment with Tafinlar (dabrafenib) and Mekinist (trametinib) in a patient with intrahepatic cholangiocarcinoma harboring BRAF V600E who progressed on chemotherapy led to stable disease at 6 weeks, improvement of lung and liver lesions at 12 weeks after treatment, and response was maintained until disease progression in the liver was observed at 10 months (PMID: 33537843). 33537843
BRAF V600E pancreatic acinar cell adenocarcinoma predicted - sensitive Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, combination treatment with Tafinlar (dabrafenib) and Mekinist (trametinib) in a patient with pancreatic acinar cell carcinoma harboring BRAF V600E who had previously progressed on chemotherapy led to a response at 8 weeks, and ongoing clinical and radiological response was still observed at 32 months of treatment (PMID: 33537843). 33537843
BRAF V600E endometrial adenocarcinoma predicted - sensitive Dabrafenib + Rabeprazole + Rifampin Case Reports/Case Series Actionable In a Phase I trial, combination treatment with Tafinlar (dabrafenib), Rabeprazol, and Rifampin in a patient with metastatic endometrial adenocarcinoma harboring BRAF V600E, that recurred 11 years after original diagnosis and was refractory to treatment with chemotherapy, led to reduction of lung metastases and pelvic tissue mass at three months, but a slight increase in pelvic mass was observed at six months (PMID: 33537843; NCT01954043). 33537843
BRAF V600E cholangiocarcinoma predicted - sensitive Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, combination treatment with Tafinlar (dabrafenib) and Mekinist (trametinib) in a patient with metastatic cholangiocarcinoma harboring BRAF V600E who progressed on chemotherapy led to a sustained metabolic response for six months (PMID: 33537843). 33537843
BRAF V600E endometrial adenocarcinoma predicted - sensitive Dabrafenib + Rabeprazole + Rifampin + Trametinib Case Reports/Case Series Actionable In a Phase I trial, the addition of Mekinist (trametinib) to the combination treatment with Tafinlar (dabrafenib), Rabeprazol, and Rifampin resulted in a maintained radiographic response of lung metastases and stable pelvic mass size in a patient with metastatic endometrial adenocarcinoma harboring BRAF V600E, which lasted for 12 months (PMID: 33537843; NCT01954043). 33537843
BRAF V600E basal cell carcinoma predicted - sensitive Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in stable disease after three months of treatment in a patient with basal cell carcinoma harboring BRAF V600E (PMID: 33537843) 33537843