Reference Detail

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	Vol	Issue	Date	Pages	Journal Short Title
Cancer chemotherapy and pharmacology	87	3	2021 Mar	437-441	Cancer Chemother Pharmacol

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	endometrial adenocarcinoma	predicted - sensitive	Dabrafenib + Rabeprazole + Rifampin	Case Reports/Case Series	Actionable	In a Phase I trial, combination treatment with Tafinlar (dabrafenib), Rabeprazole, 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	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	intrahepatic cholangiocarcinoma	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	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	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
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 combination treatment with Tafinlar (dabrafenib), Rabeprazole, 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