Cost-effectiveness analysis of additional bevacizumab to pemetrexed plus cisplatin for malignant pleural mesothelioma based on the MAPS trial

Our plain-English summary of Cost-effectiveness analysis of additional bevacizumab to pemetrexed plus cisplatin for malignant pleural mesothelioma based on the MAPS trial, by M. Zhan, H. Zheng, T. Xu, et al (Lung Cancer, 2017).

The study

• Authors: M. Zhan, H. Zheng, T. Xu, Y. Yang, Q. Li
• Journal: Lung Cancer
• Published: 2017;110:1-6
• Type of article: Randomized trial
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose: Malignant pleural mesothelioma (MPM) is a rare malignancy, and pemetrexed/cisplatin (PC) is the gold standard first-line regime. This study evaluated the cost-effectiveness of the addition of bevacizumab to PC (with maintenance bevacizumab) for unresectable MPM based on a phase III trial that showed a survival benefit compared with chemotherapy alone.

Methods: To estimate the incremental cost-effectiveness ratio (ICER) of the incorporation of bevacizumab, a Markov model based on the MAPS trial, including the disease states of progression-free survival, progressive disease and death, was used. Total costs were calculated from a Chinese payer perspective, and health outcomes were converted into quality-adjusted life year (QALY). Model robustness was explored in sensitivity analyses.

Results: The addition of bevacizumab to PC was estimated to increase the cost by $81446.69, with a gain of 0.112 QALYs, resulting in an ICER of $727202.589 per QALY. In both one-way sensitivity and probabilistic sensitivity analyses, the ICER exceeded the commonly accepted willingness-to-pay threshold of 3 times the gross domestic product per capita of China ($23970.00 per QALY). The cost of bevacizumab had the most important impact on the ICER.

Conclusions: The combination of bevacizumab with PC chemotherapy is not a cost-effective treatment option for MPM in China. Given its positive clinical value and extremely low incidence of MPM, an appropriate price discount, assistance programs and medical insurance should be considered to make bevacizumab more affordable for this rare patient population.

Copyright © 2017 Elsevier B.V. All rights reserved.

In plain English

This was a cost-effectiveness analysis: a computer model, not a study of new patients. The authors built a Markov model from the published results of the MAPS phase III trial. That trial compared pemetrexed plus cisplatin chemotherapy with the same chemotherapy plus bevacizumab, with bevacizumab maintenance, in patients with unresectable malignant pleural mesothelioma. Prices came from 2016 fees at West China Hospital, Sichuan University. The article does not look at asbestos exposure. In the model, adding bevacizumab raised the total cost per patient from $20348.62 to $101795.31 and added 0.112 quality-adjusted life years (0.845 versus 0.733). That works out to $727202.589 per quality-adjusted life year, far above the authors' threshold of $23970.00. Bevacizumab accounted for 99.41% of the cost gap, and the result stayed above the threshold in sensitivity analyses. The authors concluded that the combination was not cost-effective in China. They noted that the quality-of-life values were borrowed from lung cancer studies and that treatment durations had to be estimated.

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 Markov model (three health states: progression-free, progressive disease, death; one-month cycles; 10-year time horizon), with one-way and probabilistic sensitivity analyses
• Who was studied: Modeled patients matching the MAPS phase III trial population: patients with unresectable malignant pleural mesothelioma not previously treated with chemotherapy. Costs were set for China using 2016 fees of West China Hospital, Sichuan University. No new patients were studied.
• Exposure: Not an asbestos exposure study. The comparison was 500 mg/m2 pemetrexed plus 75 mg/m2 cisplatin every 21 days for up to 6 cycles, with or without 15 mg/kg bevacizumab, followed by bevacizumab maintenance in the bevacizumab group. The base case assumed 5 chemotherapy cycles.
• Main results:
  • Estimated total cost per patient (5 chemotherapy cycles): $101795.31 in the bevacizumab group versus $20348.62 in the chemotherapy-alone group
  • Quality-adjusted life years: 0.845 in the bevacizumab group versus 0.733 in the chemotherapy-alone group, a gain of 0.112
  • Adding bevacizumab cost $727202.589 per quality-adjusted life year gained compared with chemotherapy alone, far above the threshold of $23970.00 per QALY used for China
  • Bevacizumab expenses made up 99.41% of the cost difference between the two regimens
  • Assuming 4 or 6 chemotherapy cycles instead of 5, the cost per QALY gained was $727698.929 and $726703.580 respectively
  • In one-way sensitivity analysis, varying the bevacizumab cost by plus or minus 20% gave a cost per QALY gained ranging from $583880.056 to $873654.927
  • In probabilistic sensitivity analysis, the bevacizumab combination had no chance of being cost-effective unless the threshold rose to $600000 per QALY
  • By the authors' calculation, the bevacizumab cost would have to fall by 97.29% (to $252.94 per month) for the cost per QALY to drop to $23911.00
• The authors' conclusion: The authors concluded that adding bevacizumab to pemetrexed plus cisplatin is not a cost-effective option in China.
• Limitations the authors state:
  • The model was based on a phase III trial rather than real-world experience
  • Most trial patients (76.5%) had effectively controlled pleural effusion, which may have favored better survival
  • Mean numbers of chemotherapy cycles and durations of bevacizumab therapy were not published, so costs were estimates
  • Quality-of-life (utility) values were taken from published non-small cell lung cancer studies, not mesothelioma
  • Costs of adverse events may be underestimated; some, such as cardiovascular adverse events, could not be included

Topics

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

Medical terms in this study, explained in our Lexicon: Bevacizumab, Pemetrexed (Alimta), Cisplatin, Pleural Mesothelioma, Unresectable, Chemotherapy, Progression-Free Survival.

Related studies

• Raltitrexed plus cisplatin is cost-effective compared with pemetrexed plus cisplatin in patients with malignant pleural mesothelioma — B. Woods, N. Paracha, et al. (2012)
• Bevacizumab plus cisplatin/pemetrexed then bevacizumab alone for unresectable malignant pleural mesothelioma: A Japanese safety study — T. Nakano, K. Kuribayashi, et al. (2021)
• A multicenter phase II study of cisplatin, pemetrexed, and bevacizumab in patients with advanced malignant mesothelioma — J.E. Dowell, F.R. Dunphy, et al. (2012)
• Trimodality strategy for treating malignant pleural mesothelioma: results of a feasibility study of induction pemetrexed plus cisplatin followed by extrapleural pneumonectomy and postoperative hemithoracic radiation (Japan Mesothelioma Interest Group 0601 Trial) — S. Hasegawa, M. Okada, et al. (2016)
• First-line chemotherapy with pemetrexed plus cisplatin for malignant peritoneal mesothelioma — E. Fujimoto, T. Kijima, et al. (2017)
• A feasibility study of induction pemetrexed plus cisplatin followed by pleurectomy/decortication aimed at macroscopic complete resection for malignant pleural mesothelioma — M. Shimokawa, S. Hasegawa, et al. (2013)

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