Evaluating cost benefits of combination therapies for advanced melanoma

Evaluating cost benefits of combination therapies for advanced melanoma

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Abstract 

Background: Although a number of monoimmunotherapies and targeted therapies are available to treat BRAF+ advanced melanoma, response rates remain relatively low in the range of 22–53% with progression-free survival (PFS) in the range of 4.8–8.8 months. Recently, combination targeted therapies have improved response rates to about 66–69%, PFS to 11.0–12.6 months and overall survival (OS) to 25.1–25.6 months. While combination immunotherapies have improved response rates of 67 compared with 19–29% with monotherapies and improved PFS of 11.7 compared with 4.4–5.8 months with monotherapies, the OS benefit is yet to be established in phase 3 trials. As healthcare costs continue to rise, US payers have a predominant interest in assessing the value of available treatments. Therefore, a cost-benefit model was developed to evaluate the value of treating BRAF+ advanced melanoma with two combination therapies: nivolumab + ipilimumab (N+I) and dabrafenib + trametinib (D+T).

Scope: The model was used to estimate total costs, total costs by expenditure category, cost per month of PFS and cost per responder for the payer, and societal perspectives of treating advanced melanoma patients with the BRAF V600 mutation using combination targeted therapy (D+T) or combination immunotherapy (N+I). The model followed patients from initiation of treatment to the point of progression or death. Deterministic and probabilistic sensitivity analyses were conducted to evaluate the robustness of the results and to understand the dispersion of simulated results.

Findings: Based on a hypothetical payer with one million covered lives, it was expected that fourteen metastatic melanoma patients with the BRAF V600 mutation would be treated each year. Cost-benefit with N+I and D+T was simulated from the payer perspective. The cost per month of PFS for N+I was $22,162, while that for D+T was $17,716 (–$4,446 cost difference); the cost per responder for N+I was $388,746 and that for D+T was $282,429 (–$106,316 cost difference). The cost per month of PFS and per responder from the societal perspective resembled the patterns observed from the payer’s perspective: the cost per month of PFS for N+I was $22,843, while that for D+T was $18,283 (–$4,560 cost difference). The cost per responder for N+I was $400,695 and that for D+T was $291,473 (–$109,222 cost difference). The totals of travel and treatment time for N+I and D+T were 58 hours and 3.9 hours per patient, respectively, of which total infusion time for N+I accounted for a majority – 59% – of the 58 hours. Sensitivity analyses indicated that results were most sensitive to model inputs for median PFS, body weight, and drug cost. Moreover, D+T is likely associated with a lower cost per month of PFS and cost per responder than N+I, except at low body weights (less than 57 kg).

Conclusion: The model presented in this study was used to analyze the clinical and economic benefit of using combination therapies in advanced melanoma patients with the BRAF V600 mutation. This analysis suggests D+T therapy is associated with less patient time and lower costs relative to N+I to gain similar PFS and overall response rate (ORR) benefits.

Keywords: metastatic melanoma, BRAF V600E mutation-positive, cost-benefit model, targeted therapy, immunotherapy, dabrafenib, trametinib, combination therapy.

Abbreviations: AE, adverse event; CTLA-4, anticytotoxic, T lymphocyte–associated antigen 4; DSA, deterministic sensitivity analysis; D+T, Dabrafenib + Trametinib; HRU, health resource utilization; mPFS, median progression free survival; N+I, nivolumab + ipilimumab; NCCN, National Comprehensive Cancer Network; ORR, overall response rate; OS, overall survival; PD-1, programmed death 1; PFS, progression-free survival; PSA, probabilistic sensitivity analysis; RCT, randomized clinical trial; TOT, time on treatment

Citation: Jensen IS, Zacherle E, Blanchette CM, Zhang J, Yin W. Evaluating cost benefits of combination therapies for advanced melanoma. Drugs in Context 2016; 5: 212297. DOI: 10.7573/dic.212297

Contributions: Ivar S. Jensen programmed the model and codrafted the manuscript with Emily Zacherle, who also conducted the targeted literature search in support of the model. All authors were instrumental in the conceptual design and participated extensively in review and editing of the model and manuscript.

Potential conflicts of interest: Jie Zhang is an employee of Novartis Corporation and owns NVS stock options. Ivar S. Jensen, Emily Zacherle, and Christopher M. Blanchette have provided consulting services to Novartis. Wes Yin has provided consulting services to Precision Health Economics. The International Committee of Medical Journal Editors’ (ICMJE) Potential Conflicts of Interests form for the author is available for download at: http://www.drugsincontext.com/wp-content/uploads/2016/07/dic.212297-COI.pdf.

Funding Declaration: This study was funded by Novartis Pharmaceuticals Corporation (Hanover, NJ USA).

Copyright: Copyright © 2016 Jensen IS, Zacherle E, Blanchette CM, Zhang J, Yin W. Distributed under the terms of the Creative Commons License Deed CC BY NC ND 3.0 which allows anyone to copy, distribute, and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission.

Correct attribution: Copyright © 2016 Jensen IS, Zacherle E, Blanchette CM, Zhang J, Yin W. http://dx.doi.org/10.7573/dic.212297. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 3.0.

Article URL: http://www.drugsincontext.com/evaluating-cost-benefits-of-combination-therapies-for-advanced-melanoma

Correspondence: Ivar S. Jensen, MBA, Precision Health Economics, 101 Tremont St. Suite 400, Boston, MA 02108, USA. ivar.jensen@precisionformedicine.com

Provenance: Submitted; externally peer reviewed

Submitted: 25 May 2016; Peer review comments to author: 8 June 2016; Published: 15 July 2016

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