GlaxoSmithKline (GSK) announced that the National Institute for Health and Care Excellence (NICE) issued its final appraisal determination (FAD) recommending the use of Tafinlar® (dabrafenib) for the treatment of adults with melanoma that has been shown to have a specific mutation called ‘BRAF V600’ and has spread to other parts of the body (metastatic) or cannot be surgically removed (unresectable). (1)
GlaxoSmithKline (GSK) announced that the National Institute for Health and Care Excellence (NICE) issued its final appraisal determination (FAD) recommending the use of Tafinlar® (dabrafenib) for the treatment of adults with melanoma that has been shown to have a specific mutation called ‘BRAF V600’ and has spread to other parts of the body (metastatic) or cannot be surgically removed (unresectable). (1)
The independent NICE committee decided that an interim stage of appraisal consultation document (ACD) was not required, so the recommendations could go straight to FAD. The guidance states: “Dabrafenib is recommended, within its marketing authorisation, as an option for treating unresectable or metastatic BRAF V600 mutation-positive melanoma only if the company provides dabrafenib with the discount agreed in the patient access scheme.” (1)
Professor Ruth Plummer, Consultant Medical Oncologist, Newcastle NHS Trusts comments, “This decision is great news as it means that for patients with metastatic melanoma there is another important treatment option which extends progression free survival and provides quality of life benefits.”
Melanoma is one of the most common types of cancer in people between the ages of 15 to 34 in the UK. (2) This type of skin cancer has the highest mortality rate (causes the most skin cancer-related deaths) (3) and its incidence is increasing – between 2002 and 2011, new cases of melanoma have increased by 66%. (4) The BRAF gene mutation is seen in around 50% of cutaneous melanoma cases. (5)
“We are delighted that the NICE’s evaluation of dabrafenib has resulted in a positive recommendation, and this is testament to the strength of its clinical and cost-effectiveness evidence. We look forward to the ratification of this guidance and to implementing the agreed patient access scheme.” said Nikki Yates, General Manager of GSK UK Pharmaceuticals. “Dabrafenib represents an important treatment option that we hope clinicians will soon routinely have available to them to support patients in this challenging disease area.”
Dabrafenib received marketing authorisation from the European Commission in August 2013, based on results from one multicentre international trial, specifically the pivotal, open-label Phase III BREAK-3 study. (5) In the Phase III BREAK-3 study, dabrafenib provided patients a median of 6.9 months free from disease progression compared with 2.7 months on chemotherapy (dacarbazine) (HR=0.37, p<0.0001). (6) Furthermore, dabrafenib showed a 59% overall response rate versus only 24% with dacarbazine. (6) Dabrafenib is the only BRAF inhibitor to have reported a rapid improvement in quality of life versus dacarbazine across a range of functional and symptomatic measures. (7)
The safety profile of dabrafenib is based on data from five clinical monotherapy studies and included 578 patients with melanoma. (8) The most frequently occurring adverse drug reactions (ADRs) (≥ 15% patients) reported with dabrafenib were: hyperkeratosis (a condition causing benign skin thickening or lesions), headache, pyrexia (fever), arthralgia (joint pain), fatigue, nausea, skin papilloma (a condition causing non-cancerous skin growths), alopecia (hair loss), rash and vomiting. (8)
An FAD is the final stage in the NICE technology appraisal process before guidance is issued. The Appraisal Committee makes its final recommendations on how the technology should be used in the NHS in England. Consultees can appeal against the final recommendations in the FAD. If there are no appeals, or an appeal is not upheld, the final recommendations are issued as NICE guidance. (9)
References:
- National Institute for Health and Care Excellence (NICE). Dabrafenib for treating unresectable or metastatic BRAF V600 mutation-positive melanoma. Final Appraisal Determination September 2014. Available at: http://www.nice.org.uk/guidance/date Accessed September 2014
- Cancer Research UK. Melanoma risks and causes. Available at: http://www.cancerresearchuk.org/cancer-help/type/melanoma/about/melanoma-risks-and-causes. Accessed September 2014.
- Skin Cancer Foundation. “What Is Melanoma?” Available at http://www.skincancer.org/skin-cancer-information/melanoma. Accessed September 2014.
- Office for National Statistics, Cancer Statistics Registrations, England, No. 42, 2011 http://www.ons.gov.uk/ons/publications/re-reference-tables.html?edition=tcm%3A77-302299. Accessed September 2014.
- Hauschild A, Grob JJ, Demidov LV, et al. Dabrafenib in BRAF-Mutated Metastatic Melanoma: A Multicentre, Open-Label, Phase 3 Randomised Controlled Trial. Lancet 2012; 380: 358-65.
- Hauschild A, Grob JJ, Demidov LV, et al. An update on BREAK-3, a phase III, randomized trial: Dabrafenib (DAB) versus dacarbazine (DTIC) in patients with BRAF V600E-positive mutation metastatic melanoma (MM). Poster and abstract presented at ASCO annual meeting 2013. J Clin Oncol 2013; 31 (suppl): Abstract 9103.
- Grob JJ, Amonkar MM, Martin-Algarra S, et al. Patient Perception of the Benefit of a BRAF Inhibitor in Metastatic Melanoma: Quality of Life Analyses of the BREAK-3 Study Comparing Dabrafenib With DTIC. Ann Oncol. 2014 Epub ahead of print publication Apr 25. doi: 10.1093/annonc/mdu154
- GlaxoSmithKline. Tafinlar (dabrafenib) Summary of Product Characteristics July 2014
- NICE technology appraisal processes available at: http://www.nice.org.uk/About/What-we-do/Our-Programmes/NICE-guidance/NICE-technology-appraisal-guidance Accessed September 2014
