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Published in: PharmacoEconomics 4/2015

01-04-2015 | Original Research Article

Cost Effectiveness of Dabrafenib as a First-Line Treatment in Patients with BRAF V600 Mutation-Positive Unresectable or Metastatic Melanoma in Canada

Authors: Thomas E. Delea, Jordan Amdahl, Alice Wang, Mayur M. Amonkar, Marroon Thabane

Published in: PharmacoEconomics | Issue 4/2015

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Abstract

Objective

To evaluate the cost effectiveness of dabrafenib versus dacarbazine and vemurafenib as first-line treatments in patients with BRAF V600 mutation-positive unresectable or metastatic melanoma from a Canadian healthcare system perspective.

Methods

A partitioned-survival analysis model with three mutually exclusive health states (pre-progression, post-progression, and dead) was used. The proportion of patients in each state was calculated using survival distributions for progression-free and overall survival derived from pivotal trials of dabrafenib and vemurafenib. For each treatment, expected progression-free, post-progression, overall, and quality-adjusted life-years (QALYs), and costs were calculated. Costs were based on list prices, a clinician survey, and published sources. A 5-year time horizon was used in the base case. Costs (in 2012 Canadian dollars [CA$]) and QALYs were discounted at 5 % annually. Deterministic and probabilistic sensitivity analyses were conducted.

Results

Dabrafenib was estimated to yield 0.2055 more QALYs at higher cost than dacarbazine. The incremental cost-effectiveness ratio was CA$363,136/QALY. In probabilistic sensitivity analyses, at a threshold of CA$200,000/QALY, there was an 8.2 % probability that dabrafenib is cost effective versus dacarbazine. In deterministic sensitivity analyses, cost effectiveness was sensitive to survival distributions, utilities, and time horizon, with the hazard ratio for overall survival for dabrafenib versus dacarbazine being the most sensitive parameter. Assuming a class effect for efficacy of BRAF inhibitors, dabrafenib was dominant versus vemurafenib (less costly, equally effective), reflecting its assumed lower daily cost. Assuming no class effect, dabrafenib yielded 0.0486 more QALYs than vemurafenib.

Conclusions

At a threshold of CA$200,000/QALY, dabrafenib is unlikely to be cost effective compared with dacarbazine. It is not possible to make reliable conclusions regarding the relative cost effectiveness of dabrafenib versus vemurafenib based on available information.
Appendix
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Footnotes
1
Latimer N, Abrams K. Adjusting for treatment crossover in the BREAK-3 clinical trial—stage 1 feasibility analysis results, February 2013 update. 2013.
 
2
BioMérieux. THxID-BRAF preliminary performance for medico-economic modeling. May 25 2012.
 
Literature
1.
go back to reference Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417(6892):949–54.CrossRefPubMed Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417(6892):949–54.CrossRefPubMed
2.
go back to reference Menzies AM, Long GV, Murali R. Dabrafenib and its potential for the treatment of metastatic melanoma. Drug Des Devel Ther. 2012;6:391–405.PubMedCentralPubMed Menzies AM, Long GV, Murali R. Dabrafenib and its potential for the treatment of metastatic melanoma. Drug Des Devel Ther. 2012;6:391–405.PubMedCentralPubMed
3.
go back to reference Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507–16.CrossRefPubMedCentralPubMed Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507–16.CrossRefPubMedCentralPubMed
5.
go back to reference Chapman PB, Hauschild A, Robert C, Larkin JMG, Haanen JBAG, Ribas A, et al. Updated overall survival (OS) results for BRIM-3, a phase III randomized, open-label, multicenter trial comparing BRAF inhibitor vemurafenib (vem) with dacarbazine (DTIC) in previously untreated patients with BRAFV600E-mutated melanoma. J Clin Oncol. 2012;30(suppl 15):8502. Chapman PB, Hauschild A, Robert C, Larkin JMG, Haanen JBAG, Ribas A, et al. Updated overall survival (OS) results for BRIM-3, a phase III randomized, open-label, multicenter trial comparing BRAF inhibitor vemurafenib (vem) with dacarbazine (DTIC) in previously untreated patients with BRAFV600E-mutated melanoma. J Clin Oncol. 2012;30(suppl 15):8502.
7.
go back to reference Hauschild A, Grob JJ, Demidov LV, Jouary T, Gutzmer R, Millward M, et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2012;380(9839):358–65.CrossRefPubMed Hauschild A, Grob JJ, Demidov LV, Jouary T, Gutzmer R, Millward M, et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2012;380(9839):358–65.CrossRefPubMed
8.
go back to reference Hauschild A, Grob J-J, Demidov L, Jouary T, Gutmer R, Millward M, et al. An update on BREAK-3, a phase III, randomized trial: dabrafenib vs dacarbazine (DTIC) in patients with BRAF V600E positive mutation metastatic melanoma (MM). J Clin Oncol. 2013;31(15 suppl):9013. Hauschild A, Grob J-J, Demidov L, Jouary T, Gutmer R, Millward M, et al. An update on BREAK-3, a phase III, randomized trial: dabrafenib vs dacarbazine (DTIC) in patients with BRAF V600E positive mutation metastatic melanoma (MM). J Clin Oncol. 2013;31(15 suppl):9013.
10.
go back to reference Delea TE, Amdahl J, Chit A, Amonkar MM. Cost-effectiveness of lapatinib plus letrozole in HER2-positive, hormone receptor-positive metastatic breast cancer in Canada. Curr Oncol. 2013;20(5):e371–87.CrossRefPubMedCentralPubMed Delea TE, Amdahl J, Chit A, Amonkar MM. Cost-effectiveness of lapatinib plus letrozole in HER2-positive, hormone receptor-positive metastatic breast cancer in Canada. Curr Oncol. 2013;20(5):e371–87.CrossRefPubMedCentralPubMed
11.
go back to reference Delea TE, El Ouagari K, Rotter J, Wang A, Kaura S, Morgan GJ. Cost-effectiveness of zoledronic acid compared with clodronate in multiple myeloma. Curr Oncol. 2012;19(6):e392–403.CrossRefPubMedCentralPubMed Delea TE, El Ouagari K, Rotter J, Wang A, Kaura S, Morgan GJ. Cost-effectiveness of zoledronic acid compared with clodronate in multiple myeloma. Curr Oncol. 2012;19(6):e392–403.CrossRefPubMedCentralPubMed
14.
go back to reference Mittmann N, Evans W, Rocchi A, Longo C, Au H-J, Husereau D, et al. Addendum to CADTH’s Guidelines for the Economic Evaluation of Health Technologies: specific guidance for oncology products. Ottawa: Canadian Agency for Drugs and Technologies in Health; 2009. Mittmann N, Evans W, Rocchi A, Longo C, Au H-J, Husereau D, et al. Addendum to CADTH’s Guidelines for the Economic Evaluation of Health Technologies: specific guidance for oncology products. Ottawa: Canadian Agency for Drugs and Technologies in Health; 2009.
15.
go back to reference Srivastava K, Pathak P, Amonkar MM, Stapelkamp C, Swann R, Casey M, et al. Systematic review and indirect treatment comparison (ITC) of dabrafenib (Dab) and trametinib (Tram) versus first-line (1L) treatments for metastatic melanoma (MM) [abstract]. J Clin Oncol. 2013;31(suppl):abstract e20012. Srivastava K, Pathak P, Amonkar MM, Stapelkamp C, Swann R, Casey M, et al. Systematic review and indirect treatment comparison (ITC) of dabrafenib (Dab) and trametinib (Tram) versus first-line (1L) treatments for metastatic melanoma (MM) [abstract]. J Clin Oncol. 2013;31(suppl):abstract e20012.
16.
go back to reference Leighl NB, Shepherd FA, Kwong R, Burkes RL, Feld R, Goodwin PJ. Economic analysis of the TAX 317 trial: docetaxel versus best supportive care as second-line therapy of advanced non-small-cell lung cancer. J Clin Oncol. 2002;20(5):1344–52.CrossRefPubMed Leighl NB, Shepherd FA, Kwong R, Burkes RL, Feld R, Goodwin PJ. Economic analysis of the TAX 317 trial: docetaxel versus best supportive care as second-line therapy of advanced non-small-cell lung cancer. J Clin Oncol. 2002;20(5):1344–52.CrossRefPubMed
17.
go back to reference Mittmann N, Verma S, Koo M, Alloul K, Trudeau M. Cost effectiveness of TAC versus FAC in adjuvant treatment of node-positive breast cancer. Curr Oncol. 2010;17(1):7–16.PubMedCentralPubMed Mittmann N, Verma S, Koo M, Alloul K, Trudeau M. Cost effectiveness of TAC versus FAC in adjuvant treatment of node-positive breast cancer. Curr Oncol. 2010;17(1):7–16.PubMedCentralPubMed
22.
go back to reference Morden JP, Lambert PC, Latimer N, Abrams KR, Wailoo AJ. Assessing methods for dealing with treatment switching in randomised controlled trials: a simulation study. BMC Med Res Methodol. 2011;11:4.CrossRefPubMedCentralPubMed Morden JP, Lambert PC, Latimer N, Abrams KR, Wailoo AJ. Assessing methods for dealing with treatment switching in randomised controlled trials: a simulation study. BMC Med Res Methodol. 2011;11:4.CrossRefPubMedCentralPubMed
23.
go back to reference Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Atkins MB, Byrd DR, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol. 2009;27(36):6199–206.CrossRefPubMedCentralPubMed Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Atkins MB, Byrd DR, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol. 2009;27(36):6199–206.CrossRefPubMedCentralPubMed
24.
go back to reference Bucher HC, Guyatt GH, Griffith LE, Walter SD. The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol. 1997;50(6):683–91.CrossRefPubMed Bucher HC, Guyatt GH, Griffith LE, Walter SD. The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol. 1997;50(6):683–91.CrossRefPubMed
25.
go back to reference Tawbi HA, Kirkwood JM. Targeted therapies: BREAKing a path for progress—dabrafenib confirms class effect. Nat Rev Clin Oncol. 2012;9(9):496–7.CrossRefPubMed Tawbi HA, Kirkwood JM. Targeted therapies: BREAKing a path for progress—dabrafenib confirms class effect. Nat Rev Clin Oncol. 2012;9(9):496–7.CrossRefPubMed
27.
go back to reference Briggs AH. Handling uncertainty in cost-effectiveness models. Pharmacoeconomics. 2000;17(5):479–500.CrossRefPubMed Briggs AH. Handling uncertainty in cost-effectiveness models. Pharmacoeconomics. 2000;17(5):479–500.CrossRefPubMed
Metadata
Title
Cost Effectiveness of Dabrafenib as a First-Line Treatment in Patients with BRAF V600 Mutation-Positive Unresectable or Metastatic Melanoma in Canada
Authors
Thomas E. Delea
Jordan Amdahl
Alice Wang
Mayur M. Amonkar
Marroon Thabane
Publication date
01-04-2015
Publisher
Springer International Publishing
Published in
PharmacoEconomics / Issue 4/2015
Print ISSN: 1170-7690
Electronic ISSN: 1179-2027
DOI
https://doi.org/10.1007/s40273-014-0241-z

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