Vemurafenib for the Treatment of Locally Advanced or Metastatic BRAF V600 Mutation-Positive Malignant Melanoma: A NICE Single Technology Appraisal
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
Vemurafenib is an oral BRAF inhibitor licenced for the treatment of locally advanced or metastatic BRAF V600-mutation positive malignant melanoma. The manufacturer of vemurafenib, Roche Products Limited, was invited by the National Institute for Health and Care Excellence (NICE) to submit evidence of the drug’s clinical- and cost-effectiveness for its licenced indication, to inform the Institute’s Single Technology Appraisal (STA) process. The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG) for this appraisal. This article summarises the ERG’s review of the evidence submitted by the manufacturer and also includes a summary of the NICE Appraisal Committee (AC) decision. The ERG reviewed the clinical- and cost-effectiveness evidence in accordance with the decision problem defined by NICE. The ERG’s analysis of the submitted economic model assessed the appropriateness of the approach taken by the manufacturer in modelling the decision problem. It also included an assessment of the reliability of model implementation and the extent of conformity to published standards and prevailing norms of practice within the health economics modelling community. Particular attention was paid to issues likely to impact substantially on the base-case cost-effectiveness results. The clinical evidence was derived from BRIM 3 (BRAF Inhibitor in Melanoma 3), a well-designed, multi-centre, multi-national, phase III, randomised controlled trial (RCT). Clinical outcome results from the October 2011 data cut showed that median overall survival for patients treated with vemurafenib was 13.2 months compared with 9.6 months for those treated with dacarbazine. The ERG’s main concern with the trial was the potential for confounding because of the early introduction of the crossover from the comparator drug to vemurafenib or another BRAF inhibitor. The submitted incremental cost-effectiveness ratio (ICER) was considered above the NICE threshold, even when end-of-life criteria were taken into account. The ERG questioned the submitted economic model on a number of grounds, particularly the approach used to project trial results. After the ERG had made appropriate corrections to the model and employed an alternative form of projective modelling, the ICER per quality-adjusted life year more than doubled. Additional evidence was submitted by the manufacturer for consideration at a second AC meeting and at their third meeting the AC concluded that vemurafenib could be recommended as first-line maintenance treatment for patients with locally advanced or metastatic BRAF V600 mutation-positive malignant melanoma.
- National Institute for Health and Clinical Excellence. Guide to the single technology appraisal process. 2009. http://www.nice.org.uk/media/913/06/guide_to_the_sta-proof_6-26-10-09.pdf. Accessed 12 Sept 2013.
- National Institute for Health and Clinical Excellence. Melanoma (BRAF V600 mutation positive, unresetable metastatic) - vemurafenib (TA269). 2011. http://guidance.nice.org.uk/TA269. Accessed 12 Sept 2013.
- Dickson R, Bagust A, Boland A, Blundell M, Davis H, Dundar Y, et al. Erlotinib monotherapy for the maintenance treatment of non-small cell lung cancer after previous platinum-containing chemotherapy. Pharmacoeconomics. 2011;29(12):1–12. CrossRef
- Greenhalgh J, Bagust A, Boland A, Blundell M, Oyee J, Beale S, et al. Rituximab for the first-line maintenance treatment of follicular non-Hodgkin’s lymphoma. PharmacoEconomics. 2013;31:403–13. doi:10.1007/s40273-013-0043-8. CrossRef
- Parkin D, Mesher D, Sasieni P. Cancers attributable to solar (ultraviolet) radiation exposure in the UK in 2010. Br J Cancer. 2011;31:403–13. doi:10.1007/s40273-013-0043-8.
- Cancer Research UK. Skin cancer statistics - UK. 2011. http://info.cancerresearchuk.org/cancerstats/types/skin/. Accessed July 2011.
- American Joint Committee on Cancer. Melanoma of the skin staging. 7th ed. 2009. http://www.cancerstaging.org/staging/posters/melanoma8.5x11.pdf. Accessed 21 August 2013.
- NHS England. The Cancer Drugs Fund. http://www.england.nhs.uk/ourwork/cdf/. Accessed 26 June 2013.
- Long G, Menzies A, Nagrial A, et al. Clinico-pathologic correlates of BRAF mutation status in 207 consecutive patients with metastatic melanoma. Am Soc Clin Oncol. 2010;28(15 Suppl.): abstract 8548.
- Roche. NICE STA submission: vemurafenib for the treatment of locally advanced or metastatic BRAF V600 mutation positive malignant melanoma. 2012. http://guidance.nice.org.uk/TA/Wave27/5/Consultation/EvaluationReport/ManufacturerSubmissions/Roche/pdf/English. Accessed 5 July 2013.
- Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. New Engl J Med. 2011;364(26):2507–16. CrossRef
- Hoffmann-La Roche I. Clinical study report – BRIM 3. 2011. Data on file.
- FACITOrg. Questionnaires. http://www.facit.org/FACITOrg/Questionnaires. Accessed 26 June 2013.
- Robert C, Thomas L, Bondarenko I, O’Day S, Weber J, Garbe C, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. New Engl J Med. 2011;364(26):2517–26. CrossRef
- Xing Y, Chang G, Hu C, Askew R, Ross M, Gershenwald J, et al. Conditional survival estimates improve over time for patients with advanced melanoma. Cancer. 2010;116:2234–41.
- Beusterien KM, Szabo SM, Kotapati S, Mukherjee J, Hoos A, Hersey P, et al. Societal preference values for advanced melanoma health states in the United Kingdom and Australia. Br J Cancer. 2009;101(3):387–9. CrossRef
- Nafees B, Stafford M, Gavriel S, Bhalla S, Watkins J. Health state utilities for non small cell lung cancer. Health Qual Live Outcomes. 2008;6:84. CrossRef
- Department of Health. National schedule of reference costs 2009–2010. 2011. http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_123459. Accessed 22 March 2013.
- Joint Formulary Committee. British National Formulary. 2011.
- National Institute for Health and Clinical Excellence. Melanoma (Stage III or IV) – ipilimumab. 2012. http://guidance.nice.org.uk/TA/WaveCRS2/48. Accessed February 2012.
- Balch C, Gershenwald J, Soong S, Thompson J, Atkins M, Byrd D, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol. 2009;21:6199–206. CrossRef
- Bedikian A, DeConti R, Conry R, Agarwala S, Papadopoulos N, Kim K, et al. Phase 3 study of docosahexaenoic acid-paclitaxel versus dacarbaxine in patients with metastatic malignant melanoma. Ann Oncol. 2011;22:787–93. CrossRef
- Roche. Vemurafenib for the treatment of BRAF V600 mutation positive metastatic melanoma: manufacturer’s response to the first ACD. 2012. http://www.nice.org.uk/nicemedia/live/13579/60480/60480.pdf. Accessed 5 July 2013.
- Vemurafenib for the Treatment of Locally Advanced or Metastatic BRAF V600 Mutation-Positive Malignant Melanoma: A NICE Single Technology Appraisal
Volume 31, Issue 12 , pp 1121-1129
- Cover Date
- Print ISSN
- Online ISSN
- Springer International Publishing
- Additional Links
- Industry Sectors
- Author Affiliations
- 1. Liverpool Reviews and Implementation Group, University of Liverpool, Whelan Building, Brownlow Hill, Liverpool, L69 3GB, UK
- 2. The Clatterbridge Cancer Centre NHS Foundation Trust, Clatterbridge Road, Bebington, Wirral, CH63 4JY, UK
- 3. Northern Institute for Cancer Research, Paul O’Gorman Building, Medical School, Newcastle University, Framlington Place, NE2 4HH, Newcastle upon Tyne, UK
- 4. North West Medicines Information Centre, Pharmacy Practice Unit, 70 Pembroke Place, Liverpool, L69 3GF, UK