Clinical data | |
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Trade names | Tafinlar |
Other names | GSK-2118436 |
AHFS/Drugs.com | Monograph |
MedlinePlus | a613038 |
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Routes of administration | By mouth |
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CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.215.965 |
Chemical and physical data | |
Formula | C23H20F3N5O2S2 |
Molar mass | 519.56 g·mol−1 |
3D model (JSmol) | |
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Dabrafenib, sold under the brand name Tafinlar among others, is an anti-cancer medication used for the treatment of cancers associated with a mutated version of the gene BRAF. [2] Dabrafenib acts as an inhibitor of the associated enzyme B-Raf, which plays a role in the regulation of cell growth.
The most common side effects include papilloma (warts), headache, nausea, vomiting, hyperkeratosis (thickening and toughening of the skin), hair loss, rash, joint pain, fever and tiredness. [3] When taken in combination with trametinib, the most common side effects include fever, tiredness, nausea, chills, headache, diarrhea, vomiting, joint pain and rash. [3]
Dabrafenib was approved for medical use in the United States in May 2013, [7] and in the European Union in August 2013. [3]
Dabrafenib is indicated as a single agent for the treatment of people with unresectable or metastatic melanoma with BRAF V600E mutation. [2] Dabrafenib is indicated, in combination with trametinib, for BRAF V600E-positive unresectable or metastatic melanoma, metastatic non-small cell lung cancer, metastatic anaplastic thyroid cancer, and unresectable or metastatic solid tumors. [2] [3] [8]
Clinical trial data demonstrated that resistance to dabrafenib and other BRAF inhibitors occurs within six to seven months. [9] To overcome this resistance, the BRAF inhibitor dabrafenib was combined with the MEK inhibitor trametinib. [9] In January 2014, the FDA approved this combination of dabrafenib and trametinib for BRAF V600E/K-mutant metastatic melanoma. [10] [11] In May 2018, the FDA approved the combination dabrafenib/trametinib as an adjuvant treatment for BRAF V600E-mutated, stage III melanoma after surgical resection based on the results of the COMBI-AD phase 3 study, [12] making it the first oral chemotherapy regimen that prevents cancer relapse for node positive, BRAF-mutated melanoma. [13]
The US Food and Drug Administration approved dabrafenib as a single agent treatment for people with BRAF V600E mutation-positive advanced melanoma in May 2013. [7] [14] Dabrafenib was approved for use in the European Union in August 2013. [3]
In April 2017, the European Union approved the combination of dabrafenib with trametinib for BRAF V600-positive advanced or metastatic non small-cell lung cancer (NSCLC). [15] [16] [3]
In September 2023, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Finlee, intended for the treatment of low- and high-grade glioma (LGG and HGG). [17] The applicant for this medicinal product is Novartis Europharm Limited. [17] Finlee was approved for medical use in the European Union in November 2023. [4]
Dabrafenib is the international nonproprietary name. [18]
Dabrafenib is sold under the brand names Tafinlar [3] and Finlee. [4]
Dabrafenib has clinical activity with a manageable safety profile in clinical trials of phase I and II in patients with BRAF (V600)-mutated metastatic melanoma. [19] [20]
Bevacizumab, sold under the brand name Avastin among others, is a monoclonal antibody medication used to treat a number of types of cancers and a specific eye disease. For cancer, it is given by slow injection into a vein (intravenous) and used for colon cancer, lung cancer, ovarian cancer, glioblastoma, and renal-cell carcinoma. In many of these diseases it is used as a first-line therapy. For age-related macular degeneration it is given by injection into the eye (intravitreal).
Targeted therapy or molecularly targeted therapy is one of the major modalities of medical treatment (pharmacotherapy) for cancer, others being hormonal therapy and cytotoxic chemotherapy. As a form of molecular medicine, targeted therapy blocks the growth of cancer cells by interfering with specific targeted molecules needed for carcinogenesis and tumor growth, rather than by simply interfering with all rapidly dividing cells. Because most agents for targeted therapy are biopharmaceuticals, the term biologic therapy is sometimes synonymous with targeted therapy when used in the context of cancer therapy. However, the modalities can be combined; antibody-drug conjugates combine biologic and cytotoxic mechanisms into one targeted therapy.
Tremelimumab, sold under the brand name Imjudo, is a fully human monoclonal antibody used for the treatment of hepatocellular carcinoma. Tremelimumab is designed to attach to and block CTLA-4, a protein that controls the activity of T cells, which are part of the immune system.
Olaparib, sold under the brand name Lynparza, is a medication for the maintenance treatment of BRCA-mutated advanced ovarian cancer in adults. It is a PARP inhibitor, inhibiting poly ADP ribose polymerase (PARP), an enzyme involved in DNA repair. It acts against cancers in people with hereditary BRCA1 or BRCA2 mutations, which include some ovarian, breast, and prostate cancers.
Vemurafenib (INN), sold under the brand name Zelboraf, is a medication used for the treatment of late-stage melanoma. It is an inhibitor of the B-Raf enzyme and was developed by Plexxikon.
Nivolumab, sold under the brand name Opdivo, is an anti-cancer medication used to treat a number of types of cancer. This includes melanoma, lung cancer, malignant pleural mesothelioma, renal cell carcinoma, Hodgkin lymphoma, head and neck cancer, urothelial carcinoma, colon cancer, esophageal squamous cell carcinoma, liver cancer, gastric cancer, and esophageal or gastroesophageal junction cancer. It is administered intravenously.
Trametinib, sold under the brand name Mekinist among others, is an anticancer medication used for the treatment of melanoma and glioma. It is a MEK inhibitor drug with anti-cancer activity. It inhibits MEK1 and MEK2. It is taken by mouth.
A MEK inhibitor is a chemical or drug that inhibits the mitogen-activated protein kinase kinase enzymes MEK1 and/or MEK2. They can be used to affect the MAPK/ERK pathway which is often overactive in some cancers.
Encorafenib, sold under the brand name Braftovi, is a medication for the treatment of certain melanoma cancers. It is a small molecule BRAF inhibitor that targets key enzymes in the MAPK signaling pathway. This pathway occurs in many different cancers including melanoma and colorectal cancers. The substance was being developed by Novartis and then by Array BioPharma. In June 2018, it was approved by the FDA in combination with binimetinib for the treatment of patients with unresectable or metastatic BRAF V600E or V600K mutation-positive melanoma.
Pembrolizumab, sold under the brand name Keytruda, is a humanized antibody used in cancer immunotherapy that treats melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, stomach cancer, cervical cancer, and certain types of breast cancer. It is administered by slow intravenous injection.
Cobimetinib, sold under the brand name Cotellic, is an anti-cancer medication used in combination with vemurafenib (Zelboraf) alone or with both vemurafenib and atezolizumab (Tecentriq) to treat melanoma. Cobimetinib is a MEK inhibitor. Cotellic, Zelboraf, and Tecentriq are all marketed by Genentech.
Binimetinib, sold under the brand name Mektovi, is an anti-cancer medication used to treat various cancers. Binimetinib is a selective inhibitor of MEK, a central kinase in the tumor-promoting MAPK pathway. Inappropriate activation of the pathway has been shown to occur in many cancers. In June 2018 it was approved by the FDA in combination with encorafenib for the treatment of patients with unresectable or metastatic BRAF V600E or V600K mutation-positive melanoma. In October 2023, it was approved by the FDA for treatment of NSCLC with a BRAF V600E mutation in combination with encorafenib. It was developed by Array Biopharma.
Atezolizumab, sold under the brand name Tecentriq among others, is a monoclonal antibody medication used to treat urothelial carcinoma, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), hepatocellular carcinoma and alveolar soft part sarcoma, but discontinued for use in triple-negative breast cancer (TNBC). It is a fully humanized, engineered monoclonal antibody of IgG1 isotype against the protein programmed cell death-ligand 1 (PD-L1).
Tucatinib, sold under the brand name Tukysa, is an anticancer medication used for the treatment of HER2-positive breast cancer. It is a small molecule inhibitor of HER2. It was developed by Array BioPharma and licensed to Cascadian Therapeutics.
Ivosidenib, sold under the brand name Tibsovo, is an anti-cancer medication for the treatment of acute myeloid leukemia (AML) and cholangiocarcinoma. It is a small molecule inhibitor of isocitrate dehydrogenase-1 (IDH1), which is mutated in several forms of cancer. Ivosidenib is an isocitrate dehydrogenase-1 inhibitor that works by decreasing abnormal production of the oncometabolite 2-hydroxyglutarate (2-HG), leading to differentiation of malignant cells.
Adagrasib, sold under the brand name Krazati, is an anticancer medication used to treat non-small cell lung cancer. Adagrasib is an inhibitor of the RAS GTPase family. It is taken by mouth. It is being developed by Mirati Therapeutics.
Nivolumab/relatlimab, sold under the brand name Opdualag, is a fixed-dose combination medication use to treat melanoma. It contains nivolumab, a programmed death receptor-1 (PD-1) blocking antibody, and relatlimab, a lymphocyte activation gene-3 (LAG-3) blocking antibody. It is given by intravenous infusion.
Futibatinib, sold under the brand name Lytgobi, is an anti-cancer medication used for the treatment of cholangiocarcinoma. It is a kinase inhibitor. It is taken by mouth.
Niraparib/abiraterone acetate, sold under the brand name Akeega, is a fixed-dose combination anti-cancer medication used for the treatment of prostate cancer. It contains niraparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, and abiraterone acetate, a CYP17 inhibitor.
Lifileucel, sold under the brand name Amtagvi, is a cellular therapy used for the treatment of melanoma.