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Author Notes:

Corresponding author: Christine G. Kohn, PharmD, University of Saint Joseph School of Pharmacy & University of Connecticut/Hartford Hospital Evidence-Based Practice Center, Hartford, CT 06102; e-mail: Christine.Kohn@hhchealth.org

Conception and design: Christine G. Kohn, Simon B. Zeichner, Alberto J. Montero, Daniel A. Goldstein, Christopher R. Flowers

Financial support: Christopher R. Flowers

Administrative support: Christine G. Kohn, Christopher R. Flowers

Provision of study materials or patients: Christine G. Kohn, Simon B. Zeichner

Collection and assembly of data: Christine G. Kohn, Simon B. Zeichner, Alberto J. Montero, Christopher R. Flowers

Data analysis and interpretation: Christine G. Kohn, Simon B. Zeichner, Qiushi Chen, Alberto J. Montero, Christopher R. Flowers

Manuscript writing: All authors

Final approval of manuscript: All authors

Accountable for all aspects of the work: All authors

Christine G. Kohn No relationship to disclose

Simon B. Zeichner No relationship to disclose

Qiushi Chen No relationship to disclose

Alberto J. Montero Stock or Other Ownership: Johnson & Johnson Honoraria: Celgene Consulting or Advisory Role: New Century Health

Daniel A. Goldstein No relationship to disclose

Christopher R. Flowers Consulting or Advisory Role: OptumRxSeattle Genetics, Bayer, Gilead Sciences Research Funding: Acerta Pharma (Inst), Infinity Pharmaceuticals (Inst), Onyx Pharmaceuticals (Inst), Janssen Oncology (Inst), Gilead Sciences (Inst), Celgene (Inst), TG Therapeutics (Inst), Genentech (Inst), Pharmacyclics (Inst), AbbVie (Inst) Travel, Accommodations, Expenses: Celgene, Genentech



  • Science & Technology
  • Life Sciences & Biomedicine
  • Oncology
  • CARE

Cost-Effectiveness of Immune Checkpoint Inhibition in BRAF Wild-Type Advanced Melanoma


Journal Title:

Journal of Clinical Oncology


Volume 35, Number 11


, Pages 1194-1202

Type of Work:

Article | Final Publisher PDF


Purpose Patients who are diagnosed with stage IV metastatic melanoma have an estimated 5-year relative survival rate of only 17%. Randomized controlled trials of recent US Food and Drug Administration-approved immune checkpoint inhibitors - pembrolizumab (PEM), nivolumab (NIVO), and ipilumumab (IPI) - demonstrate improved patient outcomes, but the optimal treatment sequence in patients with BRAF wild-type metastatic melanoma remains unclear. To inform policy makers about the value of these treatments, we developed a Markov model to compare the costeffectiveness of different strategies for sequencing novel agents for the treatment of advanced melanoma. Materials and Methods We developed Markov models by using a US-payer perspective and lifetime horizon to estimate costs (2016 US$) and quality-adjusted life years (QALYs) for treatment sequences with first-line NIVO, IPI, NIVO + IPI, PEM every 2 weeks, and PEM every 3 weeks. Health states were defined for initial treatment, first and second progression, and death. Rates for drug discontinuation, frequency of adverse events, disease progression, and death obtained from randomized phase III trials were used to determine the likelihood of transition between states. Deterministic and probabilistic sensitivity analyses were conducted to evaluate model uncertainty. Results PEM every 3 weeks followed by second-line IPI was both more effective and less costly than dacarbazine followed by IPI then NIVO, or IPI followed by NIVO. Compared with the first-line dacarbazine treatment strategy, NIVO followed by IPI produced an incremental cost effectiveness ratio of $90,871/QALY, and first-line NIVO + IPI followed by carboplatin plus paclitaxel chemotherapy produced an incremental cost effectiveness ratio of $198,867/QALY. Conclusion For patients with treatment-naive BRAF wild-type advanced melanoma, first-line PEM every 3 weeks followed by second-line IPI or first-line NIVO followed by second-line IPI are the most costeffective, immune-based treatment strategies for metastatic melanoma.

Copyright information:

© 2017 by American Society of Clinical Oncology.

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