Authors' objectives: Dabrafenib (Taflinlar) is a potent and selective reversible ATP competitive BRAF kinase inhibitor. Trametinib (Mekinist) is an allosteric inhibitor of mitogen-activated extracellular signal regulated kinase 1 (MEK1) and MEK2. Dabrafenib in combination with trametinib is intended for the treatment of advanced or metastatic BRAF V600E positive non-small cell lung cancer (NSCLC) as second line therapy in patients who have received at least one prior approved platinum-based chemotherapy regimen. In a phase II clinical trial, participants in the combination treatment arm receive dabrafenib 150mg twice daily in combination with trametinib 2mg once daily and will continue on treatment until disease progression, death, or unacceptable adverse event. In the UK, lung cancer is the second most common diagnosed cancer after breast cancer, but is the most common cause of cancer death in the UK, accounting for more than 1 in 5 cancer deaths. Approximately 85-90% of all lung cancers are of the non-small cell type. The symptoms of NSCLC include haemoptysis, malaise, significant weight loss, dyspnoea and voice loss. Smoking is the main cause of lung cancer, responsible for in excess of 80% of cases. The majority of lung cancers are diagnosed in the later stages of the disease, with 48% presenting with metastases (stage IV). Around 25% of patients with advanced NSCLC receive first line chemotherapy. Around 30-40% of these patients may subsequently become candidates for second-line therapy. Research indicates that BRAF mutations are found in approximately 1-4% of NSCLCs, and of these mutations about 50% are BRAF V600E mutations. In 2013-14, there were 88,350 hospital admissions in England due to lung cancer, accounting for 108,216 finished consultant episodes and 282,717 bed days. In 2013, there were 60,848 deaths from lung cancer registered in England and Wales. The aim of treatment for locally advanced or metastatic NSCLC is to prolong survival, improve quality of life, and control disease-related symptoms. Dabrafenib in combination with trametinib is currently undergoing a phase II clinical trial comparing its effect on overall survival against treatment with dabrafenib alone. This trial is expected to complete in June 2019.

Project Status: Completed

Year Published: 2015

URL for published report: http://www.hsric.nihr.ac.uk/topics/dabrafenib-tafinlar-and-trametinib-mekinist-combination-therapy-for-metastatic-braf-v600e-positive-non-small-cell-lung-cancer/

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: England, United Kingdom

Organisation Name: NIHR Horizon Scanning Centre

Contact Address: The NIHR Horizon Scanning Centre, Department of Public Health, Epidemiology, and Biostatistics, School of Health and Population Sciences, University of Birmingham, 90 Vincent Drive, Edgbaston, Birmingham, B15 2SP. United Kingdom. Tel: +44 121 414 7831, Fax: +44 121 2269

Contact Name: c.packer@bham.ac.uk

Contact Email: c.packer@bham.ac.uk

Copyright: NIHR Horizon Scanning Research&Intelligence Centre (NIHR HSRIC)