Cost-effectiveness of nivolumab plus ipilimumab as first-line treatment for American patients with unresectable malignant pleural mesothelioma

Our plain-English summary of Cost-effectiveness of nivolumab plus ipilimumab as first-line treatment for American patients with unresectable malignant pleural mesothelioma, by Z.M. Ye, Z.Q. Tang, Z. Xu, et al (Frontiers in Public Health, 2022).

The study

• Authors: Z.M. Ye, Z.Q. Tang, Z. Xu, Q. Zhou, H. Li
• Journal: Frontiers in Public Health
• Published: 2022;10:947375
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: The treatment paradigm of unresectable malignant pleural mesothelioma (MPM) has changed in recent years. Checkmate 743 demonstrate that nivolumab plus ipilimumab showed good clinical benefits compared with chemotherapy in the treatment of MPM. The study is aim to evaluate the cost-effectiveness of Nivolumab plus ipilimumab vs. platinum plus chemotherapy for the first-line treatment of unresectable MPM.

Methods: A Markov model was developed to compare the cost and quality-adjusted life-year (QALY) of nivolumab plus ipilimumab and chemotherapy over a 10-year time horizon. Clinical efficacy and safety data were extracted from the CheckMate 743 trials. Health state utilities were obtained from published literature. Costs were collected from an US payer perspective. One-way and probabilistic sensitivity analyses were conducted to explore the impact of uncertainties on the cost-effectiveness's results.

Results: In the base case analysis, the incremental healthcare costs and QALYs for Nivolumab plus Ipilimumab vs. chemotherapy are $196,604.22 and 0.53, respectively, resulting an incremental cost-effectiveness ratio (ICER) of $372,414.28/QALYs for the model cohort of patients with locally advanced or metastatic MPM. However, Probabilistic sensitivity analysis showed that there was no probability that Nivolumab plus ipilimumab was cost-effective within the fluctuation range of other model parameters in first-line in unresectable MPM. The results of one-way sensitivity analysis showed that the cost of Nivolumab was the most sensitive parameter.

Conclusions: The ICER of Nivolumab plus ipilimumab is above the theoretical willingness-to-pay threshold in the U.S, which suggests that first-line nivolumab plus ipilimumab for unresectable MPM may be not a cost-effective choice.

Copyright © 2022 Ye, Tang, Xu, Zhou and Li.

In plain English

This was a cost-effectiveness study using a computer (Markov) model. The authors did not treat patients themselves. They drew on published results of the CheckMate 743 trial, in which 303 people with unresectable malignant pleural mesothelioma were randomized to receive nivolumab plus ipilimumab and 302 to receive platinum plus pemetrexed chemotherapy. Costs were estimated from a United States payer perspective over 10 years. In the model, nivolumab plus ipilimumab cost $292,319.48 and gave 1.11 quality-adjusted life-years (QALYs), while chemotherapy cost $95,715.26 and gave 0.58 QALYs. That was $196,604.22 more for 0.53 more QALYs, or $371,861.36 per QALY gained. This was above the authors' threshold of $207,659 per QALY. The price of nivolumab influenced the result most. When all inputs were varied together, the analysis found no probability that the combination was cost-effective at that threshold. The authors reported that a 34% price cut would bring the figure to 205,679 per QALY. They concluded the combination may be not a cost-effective choice. They noted that long-term survival was extrapolated. Quality-of-life values were taken from published values for non-small cell cancer (NSCLC).

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Cost-effectiveness analysis using a multi-state Markov model (health states: progression-free, progressed disease, death), with 3-week cycles, a 10-year time horizon, a US payer perspective and 3% discounting; one-way and probabilistic sensitivity analyses
• Who was studied: A modelled group of patients based on the CheckMate 743 trial participants with unresectable malignant pleural mesothelioma, aged 18 or older, regardless of PD-L1 expression. In the trial, 303 were randomized to nivolumab plus ipilimumab and 302 to chemotherapy
• Exposure: Not an asbestos exposure study. The article compared first-line treatments: nivolumab (3 mg/kg every 2 weeks) plus ipilimumab (1 mg/kg every 6 weeks) versus pemetrexed plus cisplatin or carboplatin chemotherapy
• Main results:
  • Nivolumab plus ipilimumab group: total cost $292,319.48 and 1.11 QALYs. Chemotherapy group: $95,715.26 and 0.58 QALYs. Incremental cost $196,604.22 for 0.53 extra QALYs
  • The incremental cost-effectiveness ratio for nivolumab plus ipilimumab versus chemotherapy was $371,861.36 per QALY, above the $207,659 threshold used
  • In one-way sensitivity analysis, the cost of nivolumab was the most influential parameter
  • In probabilistic sensitivity analysis at a threshold of $207,659 per QALY, there was no probability that nivolumab plus ipilimumab was cost-effective
  • The authors reported that reducing the cost of nivolumab plus ipilimumab by 34% gave an ICER of 205,679 per QALY, which they described as cost-effective
  • The authors stated that subgroup analyses found nivolumab plus ipilimumab was not cost-effective in any patient subgroup (subgroup results not shown in the text)
• The authors' conclusion: The authors concluded that, from the US payer perspective and compared with chemotherapy, first-line nivolumab plus ipilimumab for locally advanced or metastatic malignant pleural mesothelioma may be not a cost-effective choice at a threshold of $207,659 per QALY
• Limitations the authors state:
  • The trial did not provide long-term follow-up survival data, so survival was extrapolated and may differ from real-world patients
  • Health-state utility (quality-of-life) values came from previously published studies, not from trial patients; the methods state these were published values for non-small cell cancer (NSCLC), because no precise mesothelioma utility scores had been published
  • Only the three to four main adverse events were included for costs and utility loss
  • The model relied on CheckMate 743, which lacked further stratified analysis of epithelioid subtypes

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Nivolumab (Opdivo), Ipilimumab (Yervoy), Unresectable, Pleural Mesothelioma, CheckMate 743, Chemotherapy.

Related studies

• First-line nivolumab plus ipilimumab for unresectable MPM in China: a cost-effectiveness analysis — L. Yang, X. Song, et al. (2023)
• Five-Year Clinical Outcomes With Nivolumab Plus Ipilimumab Versus Chemotherapy as First-Line Treatment for Unresectable Pleural Mesothelioma in CheckMate 743 — A. Scherpereel, P. Baas, et al. (2026)
• Cost-effectiveness analysis of nivolumab plus ipilimumab versus chemotherapy as the first-line treatment for unresectable malignant pleural mesothelioma — L. Yang, X. Cao, et al. (2022)
• Cost Effectiveness and Budget Impact of Nivolumab Plus Ipilimumab Versus Platinum Plus Pemetrexed (with and Without Bevacizumab) in Patients with Unresectable Malignant Pleural Mesothelioma in Switzerland — M.C. Barbier, A. Fengler, et al. (2023)
• Follow-up after first-Line nivOlumab plus ipilimumab in patients with diffuse pleuRal mesotheliomA: a real-world Dutch cohort study-FLORA — L.H. Douma, M.M. Hofman, et al. (2025)
• Nivolumab or nivolumab plus ipilimumab in patients with relapsed malignant pleural mesothelioma (IFCT-1501 MAPS2): a multicentre, open-label, randomised, non-comparative, phase 2 trial — A. Scherpereel, J. Mazieres, et al. (2019)

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