First-line tremelimumab plus durvalumab and chemotherapy versus chemotherapy alone for metastatic non-small cell lung cancer: a cost-effectiveness analysis in the United States
Importance: In the open-label phase III POSEIDON randomized clinical trial (RCT), a limited course of tremelimumab plus durvalumab and chemotherapy (T + D + CT) indicated in the first-line treatment of metastatic non-small cell lung cancer (mNSCLC), progression-free survival, and overall survival (O...
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Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1163381/full |
| _version_ | 1797776290565062656 |
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| author | Wenjie Liu Gengwei Huo Peng Chen |
| author_facet | Wenjie Liu Gengwei Huo Peng Chen |
| author_sort | Wenjie Liu |
| collection | DOAJ |
| description | Importance: In the open-label phase III POSEIDON randomized clinical trial (RCT), a limited course of tremelimumab plus durvalumab and chemotherapy (T + D + CT) indicated in the first-line treatment of metastatic non-small cell lung cancer (mNSCLC), progression-free survival, and overall survival (OS) were substantially improved without significant additional tolerance burden compared to chemotherapy (CT). However, given the high cost of T + D + CT, its value needs to be evaluated in terms of both potency and cost.Objective: To evaluate the cost-effectiveness of T + D + CT versus CT in individuals with previously untreated mNSCLC from a U.S. payer perspective.Design, setting, and participants: A three-state Markov model was adopted to weigh the lifetime costs and effectiveness of T + D + CT versus CT for the treatment of first-line mNSCLC, according to the results of the POSEIDON phase III RCT involving 675 individuals with mNSCLC. Individuals were simulated to undergo either T + D + CT for up to four 21-day cycles, followed by durvalumab once every 4 weeks until disease progression or unacceptable toxic effects and one additional tremelimumab dose, or CT for up to six 21-day cycles (with or without pemetrexed maintenance; all groups) in the analysis.Main outcomes and measures: Lifetime costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) were evaluated with a willingness-to-pay (WTP) threshold of $ 100,000 to $ 150,000 per QALY. The uncertainty of the model was investigated using univariate and probabilistic sensitivity analysis.Results: T + D + CT produced additional 0.36 QALYs with additional costs of $ 217,694, compared to CT, giving rise to ICERs of $ 608,667.86/QALY. The univariate sensitivity analysis demonstrated that the outcomes were most sensitive to the cost of durvalumab. Other variables with a large or moderate influence were the utility of progression-free survival state, utility of progressive disease state, and cost of tremelimumab. Probability sensitivity analysis revealed that T + D + CT had a 0% probability of cost-effectiveness in individuals with mNSCLC at a willingness-to-pay threshold of $ 100,000 to $ 150,000 per QALY.Conclusion and relevance: In this model, T + D + CT was estimated to be less cost-effective than CT for patients with mNSCLC at a WTP threshold of $ 100,000 to $ 150,000 per QALY in the United States. When new combination therapies with remarkable effect become pivotal in the first-line treatment, the price reduction of durvalumab and tremelimumab may be necessary to achieve cost-effectiveness in future possible context. |
| first_indexed | 2024-03-12T22:48:48Z |
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| language | English |
| last_indexed | 2024-03-12T22:48:48Z |
| publishDate | 2023-07-01 |
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| spelling | doaj.art-22b26118090e4271955ee174880e65d82023-07-20T17:34:32ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-07-011410.3389/fphar.2023.11633811163381First-line tremelimumab plus durvalumab and chemotherapy versus chemotherapy alone for metastatic non-small cell lung cancer: a cost-effectiveness analysis in the United StatesWenjie LiuGengwei HuoPeng ChenImportance: In the open-label phase III POSEIDON randomized clinical trial (RCT), a limited course of tremelimumab plus durvalumab and chemotherapy (T + D + CT) indicated in the first-line treatment of metastatic non-small cell lung cancer (mNSCLC), progression-free survival, and overall survival (OS) were substantially improved without significant additional tolerance burden compared to chemotherapy (CT). However, given the high cost of T + D + CT, its value needs to be evaluated in terms of both potency and cost.Objective: To evaluate the cost-effectiveness of T + D + CT versus CT in individuals with previously untreated mNSCLC from a U.S. payer perspective.Design, setting, and participants: A three-state Markov model was adopted to weigh the lifetime costs and effectiveness of T + D + CT versus CT for the treatment of first-line mNSCLC, according to the results of the POSEIDON phase III RCT involving 675 individuals with mNSCLC. Individuals were simulated to undergo either T + D + CT for up to four 21-day cycles, followed by durvalumab once every 4 weeks until disease progression or unacceptable toxic effects and one additional tremelimumab dose, or CT for up to six 21-day cycles (with or without pemetrexed maintenance; all groups) in the analysis.Main outcomes and measures: Lifetime costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) were evaluated with a willingness-to-pay (WTP) threshold of $ 100,000 to $ 150,000 per QALY. The uncertainty of the model was investigated using univariate and probabilistic sensitivity analysis.Results: T + D + CT produced additional 0.36 QALYs with additional costs of $ 217,694, compared to CT, giving rise to ICERs of $ 608,667.86/QALY. The univariate sensitivity analysis demonstrated that the outcomes were most sensitive to the cost of durvalumab. Other variables with a large or moderate influence were the utility of progression-free survival state, utility of progressive disease state, and cost of tremelimumab. Probability sensitivity analysis revealed that T + D + CT had a 0% probability of cost-effectiveness in individuals with mNSCLC at a willingness-to-pay threshold of $ 100,000 to $ 150,000 per QALY.Conclusion and relevance: In this model, T + D + CT was estimated to be less cost-effective than CT for patients with mNSCLC at a WTP threshold of $ 100,000 to $ 150,000 per QALY in the United States. When new combination therapies with remarkable effect become pivotal in the first-line treatment, the price reduction of durvalumab and tremelimumab may be necessary to achieve cost-effectiveness in future possible context.https://www.frontiersin.org/articles/10.3389/fphar.2023.1163381/fullcost-effectivenesstremelimumabdurvalumabnon-small cell lung cancerMarkov modelPOSEIDON |
| spellingShingle | Wenjie Liu Gengwei Huo Peng Chen First-line tremelimumab plus durvalumab and chemotherapy versus chemotherapy alone for metastatic non-small cell lung cancer: a cost-effectiveness analysis in the United States Frontiers in Pharmacology cost-effectiveness tremelimumab durvalumab non-small cell lung cancer Markov model POSEIDON |
| title | First-line tremelimumab plus durvalumab and chemotherapy versus chemotherapy alone for metastatic non-small cell lung cancer: a cost-effectiveness analysis in the United States |
| title_full | First-line tremelimumab plus durvalumab and chemotherapy versus chemotherapy alone for metastatic non-small cell lung cancer: a cost-effectiveness analysis in the United States |
| title_fullStr | First-line tremelimumab plus durvalumab and chemotherapy versus chemotherapy alone for metastatic non-small cell lung cancer: a cost-effectiveness analysis in the United States |
| title_full_unstemmed | First-line tremelimumab plus durvalumab and chemotherapy versus chemotherapy alone for metastatic non-small cell lung cancer: a cost-effectiveness analysis in the United States |
| title_short | First-line tremelimumab plus durvalumab and chemotherapy versus chemotherapy alone for metastatic non-small cell lung cancer: a cost-effectiveness analysis in the United States |
| title_sort | first line tremelimumab plus durvalumab and chemotherapy versus chemotherapy alone for metastatic non small cell lung cancer a cost effectiveness analysis in the united states |
| topic | cost-effectiveness tremelimumab durvalumab non-small cell lung cancer Markov model POSEIDON |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1163381/full |
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