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

Our plain-English summary of 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, by M.C. Barbier, A. Fengler, E. Pardo, et al (PharmacoEconomics, 2023).

The study

• Authors: M.C. Barbier, A. Fengler, E. Pardo, A. Bhadhuri, N. Meier, O. Gautschi
• Journal: PharmacoEconomics
• Published: 2023;41(12):1641-1655
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural mesotheliomas (MPMs) are aggressive and often unresectable. In the past, chemotherapy was the standard for palliative treatment. However, immunotherapy with nivolumab+ipilimumab has recently received marketing approval.

Objectives: This study evaluated the cost effectiveness of nivolumab+ipilimumab versus pemetrexed+platinum (with/without bevacizumab) for Swiss patients with unresectable MPM, overall and by histological subtype.

Methods: We developed a three-state Markov cohort model with a cycle length of 1 month, a 30-year time horizon, and a discount rate of 3% per year for costs and benefits. The model included the updated survival and treatment-dependent utility results from the Checkmate-743 and MAPS registration trials. A Swiss statutory health insurance perspective was considered with unit costs for 2022 from publicly available and real-world sources. We assumed a willingness-to-pay (WTP) threshold of CHF100,000/QALY. Model robustness was explored in sensitivity and scenario analyses.

Results: Compared with chemotherapy, nivolumab+ipilimumab incurred additional costs of CHF109,115 and 0.57 additional quality-adjusted life-years (QALYs), yielding an incremental cost-effectiveness ratio (ICER) of CHF192,585/QALY (i.e. USD201,829/QALY) gained. Relative to their 2022 list price, nivolumab+ipilimumab may be cost effective if priced at 48% across all histologies. Assuming cisplatin-based instead of carboplatin-based chemotherapy reduced the ICER to CHF158,911/QALY (i.e. USD166,539/QALY). For the non-epithelioid subtype, nivolumab+ipilimumab was cost effective compared with chemotherapy (ICER of CHF97,894/QALY, i.e. USD102,593/QALY). Chemotherapy+bevacizumab was often a dominated strategy or would require a bevacizumab cost reduction to 28%.

Conclusions: Our model projected nivolumab+ipilimumab to be cost effective for the non-epithelioid subtype but not for all histologies. Substantial discounts for nivolumab+ipilimumab would be necessary to achieve cost effectiveness for all histologies.

© 2023. The Author(s).

In plain English

This was a computer-model study of a hypothetical patient group, not a new clinical trial or an asbestos-exposure study. It drew on published trial results and aggregated cost data from Swiss hospital patients. The modelled patients resembled CheckMate 743 trial participants and had malignant pleural mesothelioma that could not be removed surgically. The authors compared the costs and quality-adjusted life-years (QALYs) of nivolumab plus ipilimumab immunotherapy and pemetrexed-platinum chemotherapy with or without bevacizumab. Compared with chemotherapy, the immunotherapy cost CHF109,115 more and gave 0.57 more QALYs, which is CHF192,585 per QALY gained. This figure was CHF97,894 for the non-epithelioid subtype and CHF266,267 for the epithelioid subtype. For all subtypes combined, the authors estimated that the immunotherapy would need to be priced at 48% of its list price to be cost effective (27% for the epithelioid subtype alone), and bevacizumab at 28%. The immunotherapy was projected to raise the 5-year Swiss budget for this disease by 30% (Swissmedic label) to 45% (all patients). The authors concluded that, at a threshold of CHF100,000 per QALY, the immunotherapy was cost effective for the non-epithelioid subtype but not across all histologies.

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 and 5-year budget impact analysis using a Markov cohort computer model of a hypothetical patient population. Where available, resource use and costs were compared with aggregated real-life data from mesothelioma patients at a Swiss hospital.
• Who was studied: A hypothetical patient population modelled on the patients in the CheckMate 743 (CM-743) trial: adults with advanced, untreated, unresectable malignant pleural mesothelioma, analysed for Switzerland
• Exposure: Not an asbestos exposure study. The model compared treatments: nivolumab plus ipilimumab (immunotherapy) versus pemetrexed plus platinum chemotherapy (carboplatin in the base case), with or without bevacizumab
• Main results:
  • Over the modelled lifetime, nivolumab plus ipilimumab gave the highest mean benefit (1.78 QALYs) at the highest mean total cost (CHF184,060)
  • Chemotherapy plus bevacizumab: mean 1.59 QALYs and mean costs of CHF173,243
  • Pemetrexed plus carboplatin: mean 1.21 QALYs and mean costs of CHF74,945
  • Nivolumab plus ipilimumab versus pemetrexed plus carboplatin (all patients): 0.57 extra QALYs and CHF109,115 extra cost, an ICER of CHF192,585 (USD201,829) per QALY gained
  • Non-epithelioid subtype: ICER of CHF97,894 (USD102,593) per QALY gained for nivolumab plus ipilimumab versus pemetrexed plus carboplatin
  • Epithelioid subtype: ICER of CHF266,267 (USD279,048) per QALY gained
  • Scenario assuming cisplatin-based (inpatient) instead of carboplatin-based chemotherapy: ICER of CHF158,911 (USD166,539) per QALY gained for nivolumab plus ipilimumab
  • At a threshold of CHF100,000 per QALY, nivolumab plus ipilimumab and chemotherapy plus bevacizumab each had a 0% probability of being cost effective in the probabilistic analysis
  • For the overall population (all histologies combined), nivolumab plus ipilimumab would need a 52% price reduction, to 48% of 2022 list prices, to be cost effective
  • For the epithelioid population alone, nivolumab plus ipilimumab would need a 73% discount, to 27% of pack prices, to be cost effective (Table 2)
  • Bevacizumab would need a price reduction of 72% (to 28%) for chemotherapy plus bevacizumab to be cost effective versus pemetrexed plus carboplatin
  • Budget impact over 5 years (2022 to 2026), compared with no nivolumab plus ipilimumab: increase of 30% (CHF38.4 million) under the Swissmedic label and 45% if all patients were treated
• The authors' conclusion: The authors concluded that, at current Swiss list prices and a threshold of CHF100,000 per QALY, nivolumab plus ipilimumab is cost effective for the non-epithelioid subtype but not for all histologies. They also concluded that substantial discounts would be needed for all histologies, and that chemotherapy plus bevacizumab is unlikely to be cost effective.
• Limitations the authors state:
  • Because the MAPS trial population differed, the chemotherapy plus bevacizumab arm was simulated, which introduced a bias that overestimated its overall survival benefit during the first 6 months
  • There were no published MAPS hazard ratios for the histological subtypes
  • Utility (quality of life) during progression-free survival may be overestimated in the chemotherapy plus bevacizumab arm
  • Second- and third-line treatment was modelled from the authors' own clinical experience because reliable Swiss real-world data were lacking
  • The scenario with a maximum 24-month treatment duration should be interpreted with caution
  • Survival curves could not be adjusted for treatment switching because individual patient data were not available

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), Pemetrexed (Alimta), Bevacizumab, Unresectable, Pleural Mesothelioma, Chemotherapy, Palliative Care.

Related studies

• First-line nivolumab plus ipilimumab for unresectable MPM in China: a cost-effectiveness analysis — L. Yang, X. Song, et al. (2023)
• Cost-effectiveness of nivolumab plus ipilimumab as first-line treatment for American patients with unresectable malignant pleural mesothelioma — Z.M. Ye, Z.Q. Tang, et al. (2022)
• 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 analysis of additional bevacizumab to pemetrexed plus cisplatin for malignant pleural mesothelioma based on the MAPS trial — M. Zhan, H. Zheng, et al. (2017)
• 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 bevacizumab combined with lomustine in the treatment of progressive glioblastoma using a Markov model simulation analysis — Z. Chen, F. Tian, et al. (2024)

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