Keywords
economic evaluation
non-small cell lung cancer
NSCLC
PD-1/PD-L1 inhibitors
systematic review
Abstract
Objectives: To summarize evidence on the cost-effectiveness of PD-(L)1 inhibitors as first-line therapy in patients with high PD-L1 expression non-small cell lung cancer.
Methods: A systematic review following the PRISMA guidelines was conducted, searching PubMed, Embase, Scopus, and health technology assessment agency websites up to September 24, 2022. Eligible studies evaluated the economic outcomes of PD-(L)1 inhibitors as first-line treatment for high PD-L1 expression non-small cell lung cancer. Study quality was assessed using the CHEERS and QHES checklists
Results: 17 eligible studies were included, mostly from high-income countries (HICs), using model-based analyses from healthcare system or third-party payer perspectives. Pembrolizumab was cost-effective compared to chemotherapy in most HICs, except Singapore, but not against pembrolizumab-platinum combinations in Sweden. In China, its cost-effectiveness was uncertain. Cemiplimab was cost-effective compared to pembrolizumab or chemotherapy in the US. Atezolizumab showed inconsistent results depending on willingness-to-pay (WTP) thresholds in the US and China. Drug price significantly impacted cost-effectiveness results. Quality scores ranged from 18–22.5/28 (CHEERS) and 71.5–92.5/100 (QHES).
Conclusion: Cost-effectiveness of PD-(L)1 inhibitors for the first-line NSCLC treatment varied by country, comparator, model setting, and WTP. Policymakers should use country- and healthcare system-specific economic evaluation to guide their decision-making on resource allocation.
References
[1]
Le Thuong Vu. Bước Đầu Sử Dụng Điều Trị Nhắm Trúng Đích Cho Ung Thư Phổi Không Tế Bào Nhỏ Giai Đoạn Tiến Xa Tại Khoa Phổi BV Chợ Rẫy. Y Hoc TP Hồ Chí Minh. 2009;13:98 - 107.
Google Scholar
[2]
T. Hanagiri K. Yasumoto, M. Takenoyama. Lung cancer-associated tumor antigens and the present status of immunotherapy against non-small-cell lung cancer. Gen Thorac Cardiovasc Surg. 2009;57:449 - 57.
Google Scholar
[3]
Jiang C Zhou K, Li Q;. Cost-effectiveness analysis of pembrolizumab monotherapy and chemotherapy in the non-small-cell lung cancer with different PD-L1 tumor proportion scores. . Lung Cancer. 2019(136):98-101.
Google Scholar
[4]
Kang S Liu G, Wang X, Shang F;. Cost-Effectiveness Analysis of Atezolizumab Versus Chemotherapy as First-Line Treatment for Metastatic Non-Small-Cell Lung Cancer With Different PD-L1 Expression Status. Front Oncol. 2021.
Google Scholar
[5]
Huang J Liao W, Hutton D, Li Q;. Cost-effectiveness analysis of first-line pembrolizumab treatment for PD-L1 positive, nonsmall cell lung cancer in China. J Med Econ. 2019;22:344-9.
Google Scholar
[6]
Pei R Cheng S, Li J, Li B, Tang L, Yin T, Liu S;. Atezolizumab compared to chemotherapy for first-line treatment in non-small cell lung cancer with high PD-L1 expression: a cost-effectiveness analysis from US and Chinese perspectives. Ann Transl Med. 2021;9:1481.
Google Scholar
[7]
Tan LE Aziz MIA, Tan WHG, Toh CK, Loke LPY, Pearce F, Ng K. Cost-effectiveness analysis of pembrolizumab monotherapy versus chemotherapy for previously untreated advanced non-small cell lung cancer. J Med Econ. 2020;23:92 - 960.
Google Scholar
[8]
Pardo E Barbier MC, Panje CM, Gautschi O, Lupatsch JE; . A cost-effectiveness analysis of pembrolizumab with or without chemotherapy for the treatment of patients with metastatic, non-squamous non-small cell lung cancer and high PD-L1 expression in Switzerland. Eur J Health Econ. 2021;22:669-77.
Google Scholar
[9]
Insinga R Bhadhuri A, Guggisberg P, Panje C, Schwenkglenks M;. Cost effectiveness of pembrolizumab vs chemotherapy as first-line treatment for metastatic NSCLC that expresses high levels of PD-L1 in Switzerland. Swiss Med Wkly.2019.
Google Scholar
[10]
Lionel Bensimon Christos Chouaid, Emilie Clay, Aurélie Millier, Laurie Levy-Bachelot, Min Huang, Pierre Levy,. 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.
Google Scholar
[11]
Palazzo L Criss SD, Watson TR, Paquette AM, Sigel K, Wisnivesky J, Kong CY;. Cost-effectiveness of pembrolizumab for advanced non-small cell lung cancer patients with varying comorbidity burden. PLoS One. 2020.
Google Scholar
[12]
da Silveira Nogueira Lima JP Georgieva M, 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.
Google Scholar
[13]
Lopes GL Huang M, Insinga RP, Burke T, Ejzykowicz F, Zhang Y, Feliciano JL. Cost-effectiveness of pembrolizumab versus chemotherapy as first-line treatment in PD-L1-positive advanced non-small-cell lung cancer in the USA. Immunotherapy. 2019;11:1463-78.
Google Scholar
[14]
Lou Y Huang M, Pellissier J, Burke T, Liu FX, Xu R, Velcheti V;. Cost-effectiveness of pembrolizumab versus docetaxel for the treatment of previously treated PD-L1 positive advanced NSCLC patients in the United States. J Med Econ. 2017;20:140-50.
Google Scholar
[15]
Hu H She L, Liao M, Xia X, Shi Y, Yao L, Ding D, Zhu Y, Zeng S, Shen L, Huang J, Carbone DP;. Cost-effectiveness analysis of pembrolizumab versus chemotherapy as firstline treatment in locally advanced or metastatic non-small cell lung cancer with PD-L1 tumor proportion score 1% or greater. Lung Cancer. 2019.
Google Scholar
[16]
Shaohong Luo Xiuhua Weng, Shen Lin, Lixian Zhong, Meiyue Li, Rao Xin,Pinfang Huang,* and Xiongwei Xu. Cost–Utility Analysis of Pembrolizumab Versus Chemotherapy as First-Line Treatment for Metastatic Non-Small Cell Lung Cancer With Different PD-L1 Expression Levels. Oncology Research. 2020;28:117 - 25.
Google Scholar
[17]
Zeng X Peng Y, Peng L, Liu Q, Yi L, Luo X, Li S, Wang L, Qin S, Wan X, Tan C;. First-Line Atezolizumab for Metastatic NSCLC with High PD-L1 Expression: A United States-Based Cost-Effectiveness Analysis. Adv Ther. 2021;38:2447-57.
Google Scholar
[18]
Smare C Kuznik A, Chen CI, Venkatachalam M, Keeping S, Atsou K, Xu Y, Wilson F, Guyot P, Chan K, Glowienka E, Konidaris G;. Cost-Effectiveness of Cemiplimab Versus Standard of Care in the United States for First-Line Treatment of Advanced Non-small Cell Lung Cancer With Programmed Death-Ligand 1 Expression ≥50. Value Health. 2022;25:203-14.
Google Scholar
[19]
Liu X Zhang M, Wen F, Wu Q, Zhou K, Bai L, Li Q;. First-line Cemiplimab versus Standard Chemotherapy in Advanced Non-small Cell Lung Cancer Patients with at Least 50% Programmed Cell Death Receptor Ligand-1 Positivity: Analysis of Cost-effectiveness. Clin Oncol (R Coll Radiol). 2022.
Google Scholar
[20]
National Institute for Health and Care Excellence. Pembrolizumab for untreated PD-L1-positive metastatic non-small-cell lung cancer. 2018.
Google Scholar
[21]
National Institute for Health and Care Excellence. Atezolizumab monotherapy for untreated advanced non-small-cell lung cancer. 2021.
Google Scholar
[22]
Martin Reck, Delvys Rodríguez-Abreu, Andrew G. Robinson, et al. Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer. 2016;375(19):1823-33.
Google Scholar
[23]
Feeny D Laupacis A, Detsky AS, Tugwell PX. , 81. How attractive does a new technology have to be to warrant adoption and utilization? Tentative guidelines for using clinical and economic evaluations. Canadian Medical Association Journal. 1992;146(473).
Google Scholar
[24]
Tony S. K. Mok, Yi-Long Wu, Iveta Kudaba, et al. 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. The Lancet. 2019;393(10183):1819-30.
Google Scholar
[25]
Canadian Agency For Drugs And Technologies In Health. Pembrolizumab - pCODR expert review committee. Final recommendation. 2017.
Google Scholar
[26]
Canadian Agency For Drugs And Technologies In Health. CADTH Reimbursement Recommendation - Cemiplimab (Libtayo). 2022.
Google Scholar
[27]
Ahmet Sezer, Saadettin Kilickap, Mahmut Gümüş, et al. Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. The Lancet. 2021;397(10274):592-604.
Google Scholar