Cost effectiveness of pembrolizumab vs chemotherapy as first-line treatment for metastatic NSCLC that expresses high levels of PD-L1 in Switzerland
The study aim was to evaluate the cost effectiveness of pembrolizumab monotherapy compared with chemotherapy as a first-line treatment for previously untreated metastatic non-small cell lung cancer (NSCLC) with programmed death ligand-1 (PD-L1) tumour proportion score (TPS) ≥50%, from a Swiss payer perspective. Cost effectiveness of pembrolizumab for this indication has not previously been evaluated in Switzerland.
We conducted an analysis using a partitioned survival model with a cycle length of one week, base-case time horizon of 20 years and discount rate of 3% for cost and health outcomes. KEYNOTE-024 randomised controlled trial data for pembrolizumab monotherapy compared with chemotherapy was used as a basis for projecting time-on-treatment, progression-free survival and overall survival, over a 20-year period. For overall survival and progression-free survival, we used Kaplan-Meier probabilities for a brief initial period of the model, followed by parametric curves that had the best fit with subsequent trial data. Quality-adjusted life years (QALYs) were calculated based on the EuroQol 5-dimensional 3-level (EQ-5D-3L) questionnaire administered to trial patients. Costs (in CHF, year 2018) of drug acquisition/administration, adverse events and disease management were included.
For the base-case, pembrolizumab monotherapy resulted in mean incremental costs of CHF 77,060 (pembrolizumab CHF 223,324, chemotherapy CHF 146,264) and mean incremental QALYs of 1.34 (pembrolizumab 3.05, chemotherapy 1.71), leading to an incremental cost-effectiveness ratio of CHF 57,402 per QALY gained. Cost-effectiveness results were most sensitive to overall survival and relatively insensitive to other parameters varied. In probabilistic sensitivity analysis, the probability of cost effectiveness of pembrolizumab, with an assumption of a willingness-to-pay threshold of CHF 100,000 per QALY gained, was 88%.
Pembrolizumab is likely to be cost effective for treating Swiss patients with previously untreated metastatic NSCLC expressing PD-L1 TPS ≥50%. (This economic evaluation was based on the KEYNOTE-024 trial. The trial identifier is NCT02142738.)
- NICER and Swiss Federal Statistical Office (BFS). Lung cancer 2018 Available from: https://www.bfs.admin.ch/bfs/de/home/statistiken/gesundheit/gesundheitszustand/krankheiten/krebs/spezifische.assetdetail.6466432.html. Accessed on.
- American Cancer Society. What Is Non-Small Cell Lung Cancer? 2018 Available from: https://www.cancer.org/cancer/non-small-cell-lung-cancer/about/what-is-non-small-cell-lung-cancer.html. Accessed on 17th October 2018.
- Decision Resources Group. Non-Small-Cell Lung Cancer. 2015.
- Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, et al.; KEYNOTE-001 Investigators. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372(21):2018–28. doi:.https://doi.org/10.1056/NEJMoa1501824
- Bundesamt für Gesundheit BAG. Spezialitätenliste (SL) 2018 [Available from: http://bag.e-mediat.net/SL2007.Web.External/. Accessed on 16th October 2018.
- Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, et al. Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater. J Clin Oncol. 2019;37(7):537–46. doi:.https://doi.org/10.1200/JCO.18.00149
- Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, et al.; KEYNOTE-024 Investigators. Pembrolizumab versus chemotherapy for PD-L1–positive non–small-cell lung cancer. N Engl J Med. 2016;375(19):1823–33. doi:.https://doi.org/10.1056/NEJMoa1606774
- Huang M, Lou Y, Pellissier J, Burke T, Liu FX, Xu R, et al. Cost Effectiveness of Pembrolizumab vs. Standard-of-Care Chemotherapy as First-Line Treatment for Metastatic NSCLC that Expresses High Levels of PD-L1 in the United States. Pharmacoeconomics. 2017;35(8):831–44. doi:.https://doi.org/10.1007/s40273-017-0527-z
- Kim R, Keam B, Hahn S, Ock CY, Kim M, Kim TM, et al. First-line Pembrolizumab Versus Pembrolizumab Plus Chemotherapy Versus Chemotherapy Alone in Non-small-cell Lung Cancer: A Systematic Review and Network Meta-analysis. Clin Lung Cancer. 2019;20(5):331–338.e4. doi:.https://doi.org/10.1016/j.cllc.2019.05.009
- National Institute for Cancer Epidemiology and Registration (NICER) 2018 Available from: http://www.nicer.org/. Accessed on 1st December 2018.
- Swiss DRG. Fallkostenstatistik 2014. 2014 Available from: http://www.swissdrg.org/de. Accessed on 16th October 2018.
- Solutions HCI. Keytruda 2018 Available from: https://compendium.ch/mpro/mnr/26788/html/de. Accessed on 27th November 2018.
- Azzoli CG, Temin S, Aliff T, Baker S, Jr, Brahmer J, Johnson DH, et al.; American Society of Clinical Oncology. 2011 Focused Update of 2009 American Society of Clinical Oncology Clinical Practice Guideline Update on Chemotherapy for Stage IV Non-Small-Cell Lung Cancer. J Clin Oncol. 2011;29(28):3825–31. doi:.https://doi.org/10.1200/JCO.2010.34.2774
- Matter-Walstra K, Schwenkglenks M, Aebi S, Dedes K, Diebold J, Pietrini M, et al.; Swiss Group for Clinical Cancer Research. A cost-effectiveness analysis of nivolumab versus docetaxel for advanced nonsquamous NSCLC including PD-L1 testing. J Thorac Oncol. 2016;11(11):1846–55. doi:.https://doi.org/10.1016/j.jtho.2016.05.032
- Latimer N. NICE DSU technical support document 14: survival analysis for economic evaluations alongside clinical trials-extrapolation with patient-level data. Sheffield, UK: Report by the Decision Support Unit; 2011.
- Latimer NR, Abrams KR. NICE DSU Technical Support Document 16: adjusting survival time estimates in the presence of treatment switching. Sheffield, UK: School of Health and Related Research, University of Sheffield; 2014:b12.
- Matter-Walstra K, Klingbiel D, Szucs T, Pestalozzi BC, Schwenkglenks M. Using the EuroQol EQ-5D in Swiss cancer patients, which value set should be applied? Pharmacoeconomics. 2014;32(6):591–9. doi:.https://doi.org/10.1007/s40273-014-0151-0
- Swiss Federal Statistical Office. Consumer Prices 2018 [Available from: https://www.bfs.admin.ch/bfs/en/home/statistics/prices/consumer-price-index.html. Accessed on 16th December 2018.
- International Monetary Fund. Inflation 2019 [Available from: https://www.imf.org/external/datamapper/datasets/WEO. Accessed on 26th April 2019.
- National Institute for Health and Care Excellence. Pembrolizumab for untreated PD-L1-positive metastatic non-small-cell lung cancer 2018 [Available from: https://www.nice.org.uk/guidance/ta531. Accessed on 16th October 2018.
- Tan W, Huang M, Chandwani S, Hsu T, Tan S, Tan D, eds. Cost-effectiveness of Pembrolizumab as 1st Line Treatment for Metastatic NSCLC Patients with High PD-L1 Expression in Singapore. IASLC 19th World Conference on Lung Cancer; 2018; Toronto.
- Garon EB, Hellmann MD, Rizvi NA, Carcereny E, Leighl NB, Ahn M-J, et al. Five-Year Overall Survival for Patients With Advanced Non‒Small-Cell Lung Cancer Treated With Pembrolizumab: Results From the Phase I KEYNOTE-001 Study. J Clin Oncol. 2019;37(28):2518–27. doi:.https://doi.org/10.1200/JCO.19.00934
- Marseille E, Larson B, Kazi DS, Kahn JG, Rosen S. Thresholds for the cost-effectiveness of interventions: alternative approaches. Bull World Health Organ. 2015;93(2):118–24. doi:.https://doi.org/10.2471/BLT.14.138206
- Georgieva M, da Silveira Nogueira Lima JP, Aguiar P, Jr, de Lima Lopes G, Jr, Haaland B. Cost-effectiveness of pembrolizumab as first-line therapy for advanced non-small cell lung cancer. Lung Cancer. 2018;124:248–54. doi:.https://doi.org/10.1016/j.lungcan.2018.08.018
- Loong HH, Wong CKH, Leung LKS, Dhankhar P, Insinga RP, Chandwani S, et al. Cost Effectiveness of PD-L1-Based Test-and-Treat Strategy with Pembrolizumab as the First-Line Treatment for Metastatic NSCLC in Hong Kong. Pharmacoeconom Open. 2019. doi:. [Epub ahesd of print]https://doi.org/10.1007/s41669-019-00178-7
- Chouaid C, Bensimon L, Clay E, Millier A, Levy-Bachelot L, Huang M, et al. Cost-effectiveness analysis of pembrolizumab versus standard-of-care chemotherapy for first-line treatment of PD-L1 positive (>50%) metastatic squamous and non-squamous non-small cell lung cancer in France. Lung Cancer. 2019;127:44–52. doi:.https://doi.org/10.1016/j.lungcan.2018.11.008
- Liao W, Huang J, Hutton D, Li Q. Cost-effectiveness analysis of first-line pembrolizumab treatment for PD-L1 positive, non-small cell lung cancer in China. J Med Econ. 2019;22(4):344–9. doi:.https://doi.org/10.1080/13696998.2019.1570221
- Hu X, Hay JW. First-line pembrolizumab in PD-L1 positive non-small-cell lung cancer: A cost-effectiveness analysis from the UK health care perspective. Lung Cancer. 2018;123:166–71. doi:.https://doi.org/10.1016/j.lungcan.2018.07.012
- Mok TSK, Wu YL, Kudaba I, Kowalski DM, Cho BC, Turna HZ, et al.; KEYNOTE-042 Investigators. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet. 2019;393(10183):1819–30. doi:.https://doi.org/10.1016/S0140-6736(18)32409-7
- Gandhi L, Rodríguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, et al.; KEYNOTE-189 Investigators. Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. N Engl J Med. 2018;378(22):2078–92. doi:.https://doi.org/10.1056/NEJMoa1801005
- Paz-Ares L, Luft A, Vicente D, Tafreshi A, Gümüş M, Mazières J, et al.; KEYNOTE-407 Investigators. Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer. N Engl J Med. 2018;379(21):2040–51. doi:.https://doi.org/10.1056/NEJMoa1810865
- Insinga RP, Vanness DJ, Feliciano JL, Vandormael K, Traore S, Ejzykowicz F, et al. Cost-effectiveness of pembrolizumab in combination with chemotherapy versus chemotherapy and pembrolizumab monotherapy in the first-line treatment of squamous non-small-cell lung cancer in the US. Curr Med Res Opin. 2019;35(7):1241–56. doi:.https://doi.org/10.1080/03007995.2019.1571297
- Williams C, Lewsey JD, Mackay DF, Briggs AH. Estimation of Survival Probabilities for Use in Cost-effectiveness Analyses: A Comparison of a Multi-state Modeling Survival Analysis Approach with Partitioned Survival and Markov Decision-Analytic Modeling. Med Decis Making. 2017;37(4):427–39. doi:.https://doi.org/10.1177/0272989X16670617