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. 2024 May 10;19(5):e0302548.
doi: 10.1371/journal.pone.0302548. eCollection 2024.

Cost-effectiveness of avelumab first-line maintenance therapy for adult patients with locally advanced or metastatic urothelial carcinoma in France

Fanny Porte  1 , Anna Granghaud  2 , Jane Chang  3 , Mairead Kearney  4 , Aya Morel  2 , Ingrid Plessala  5 , Hélène Cawston  5 , Julie Roiz  6 , Ying Xiao  6 , Marie-Noelle Solbes  7 , Prisca Lambert  8 , Alain Ravaud  9 , Yohann Loriot  10 , Antoine Thiery-Vuillemin  11 , Pierre Lévy  12
Affiliations

Cost-effectiveness of avelumab first-line maintenance therapy for adult patients with locally advanced or metastatic urothelial carcinoma in France

Fanny Porte et al. PLoS One. .

Abstract

Background: This study evaluated the cost-effectiveness of avelumab first-line (1L) maintenance therapy plus best supportive care (BSC) versus BSC alone for adults with locally advanced or metastatic urothelial carcinoma (la/mUC) that had not progressed following platinum-based chemotherapy in France.

Methods: A three-state partitioned survival model was developed to assess the lifetime costs and effects of avelumab plus BSC versus BSC alone. Data from the phase 3 JAVELIN Bladder 100 trial (NCT02603432) were used to inform estimates of clinical and utility values considering a 10-year time horizon and a weekly cycle length. Cost data were estimated from a collective perspective and included treatment acquisition, administration, follow-up, adverse event-related hospitalization, transport, post-progression, and end-of-life costs. Health outcomes were measured in quality-adjusted life-years (QALYs) and life-years gained. Costs and clinical outcomes were discounted at 2.5% per annum. Incremental cost-effectiveness ratios (ICERs) were used to compare cost-effectiveness and willingness to pay in France. Uncertainty was assessed using a range of sensitivity analyses.

Results: Avelumab plus BSC was associated with a gain of 2.49 QALYs and total discounted costs of €136,917; BSC alone was associated with 1.82 QALYs and €39,751. Although avelumab plus BSC was associated with increased acquisition costs compared with BSC alone, offsets of -€20,424 and -€351 were observed for post-progression and end-of-life costs, respectively. The base case analysis ICER was €145,626/QALY. Sensitivity analyses were consistent with the reference case and showed that efficacy parameters (overall survival, time to treatment discontinuation), post-progression time on immunotherapy, and post-progression costs had the largest impact on the ICER.

Conclusions: This analysis demonstrated that avelumab plus BSC is associated with a favorable cost-effectiveness profile for patients with la/mUC who are eligible for 1L maintenance therapy in France.

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Conflict of interest statement

F. Porte is an employee of Merck Santé S.A.S., Lyon, France, an affiliate of Merck KGaA, Darmstadt, Germany at the time of the project. A. Granghaud was an employee of Pfizer S.A.S., Paris, France at the time of the study. J. Chang is an employee of Pfizer and holds stock and other ownership interest with Bayer, Bristol Myers Squibb, and Pfizer. M. Kearney is an employee of Merck KGaA, Darmstadt, Germany, and holds stock in Merck KGaA, Darmstadt, Germany, Novartis and UCB. A. Morel is an employee of Pfizer S.A.S., Paris, France. I. Plessala was an employee of Amaris Consulting, Paris, France at the time of the study. H. Cawston is an employee of Amaris Consulting, Paris, France. J. Roiz is an employee of and reposts stocks and other ownership interest with Evidera. Y. Xiao is an employee of Evidera. M.-N. Solbes is an employee of Merck Santé S.A.S., Lyon, France, an affiliate of Merck KGaA, Darmstadt, Germany. P. Lambert is an employee of Pfizer S.A.S., Paris, France. A. Ravaud has received grants or contracts from Merck KGaA, Darmstadt, Germany, and Pfizer; has received travel and accommodation expenses from Ipsen Merck KGaA, Darmstadt, Germany, Merck & Co., Kenilworth, NJ, and Pfizer; and has participated in advisory boards for Esai, Ipsen, Merck KGaA, Darmstadt, Germany, and Pfizer. Y. Loriot has served in consulting or advisory roles for Astellas Pharma, Bristol Myers Squibb, Immunomedics, Janssen, Loxo/Lilly, Merck KGaA, Darmstadt, Germany, Merck & Co., Kenilworth, NJ, Pfizer, Roche, Seattle Genetics, and Taiho Pharmaceutical; has received travel and accommodations expenses from Astellas Pharma, Janssen Oncology, Merck & Co., Kenilworth, NJ, Roche, and Seattle Genetics; and has received institutional research funding from Astellas Pharma, Basilea, Bristol Myers Squibb, Exelixis, Gilead Sciences, Incyte, Janssen Oncology, Merck KGaA, Darmstadt, Germany, Merck & Co., Kenilworth, NJ, Nektar, Pfizer, Roche, Sanofi, Seattle Genetics, and Taiho Pharmaceutical. A. Thiery-Vuillemin has participated in advisory boards for Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Ipsen, Janssen, Merck & Co., Kenilworth, NJ, Novartis, Pfizer, Roche/Genentech and Sanofi; reports employment by Bristol Myers Squibb; has served on steering committees for AstraZeneca, Bristol-Myers Squibb and Novartis; has received institutional research funding from Bayer, Ipsen and Pfizer; has served as principal investigator for Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Excelixis, Incyte, Ipsen, Johnson & Johnson, Merck & Co., Kenilworth, NJ, Novartis, Pfizer, Roche, Sanofi, and UNICANCER/GETUG; has received travel and accommodation expenses from Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Ipsen, Johnson & Johnson, Merck & Co., Kenilworth, NJ, Pfizer and Roche; and is a member of ASCO and GETUG. P. Lévy has served in consulting or advisory role and had received honoraria from Merck KGaA, Darmstadt, Germany. This does not alter our adherence to PLOS ONE policies on sharing data and materials

Figures

Fig 1
Fig 1. Current recommendations for the 1L treatment of la/mUC.
1L, first-line; AFU, French Urological Association; CR, complete response; DDMVAC: dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin; EAU, European Association of Urology; EMA, European Medicines Agency; ESMO, European Society for Medical Oncology; FDA, US Food and Drug Administration; GFR, glomerular filtration rate; la/mUC, locally advanced or metastatic urothelial carcinoma; MCBS, Magnitude of Clinical Benefit Scale; NCCN, National Comprehensive Cancer Network; PD-L1, programmed death-ligand 1; PS, performance status; PR, partial response; SD, stable disease. a Maintenance therapy with avelumab only if there is no progression with 1L platinum-containing chemotherapy. bCreatinine clearance grade 2 and New York Heart Association class III heart failure. c Rechallenge with platinum-based chemotherapy may be considered if progression occurred 12 months after the end of previous platinum-based chemotherapy or 12 months after the end of previous platinum-based chemotherapy and avelumab maintenance therapy. d This should be assessed within 10 weeks of completion of chemotherapy. e ESMO-MCBS v1.1120 was used to calculate scores for new therapies and indications approved by the EMA or the FDA. The scores have been calculated by the ESMO-MCBS Working Group and validated by the ESMO Guidelines Committee (https://www.esmo.org/guidelines/esmo-mcbs/scale-evaluation-forms-v1.0-v1.1/scale-evaluationforms-v1.1). f Fit patient: creatinine clearance ≥60 mL/min and PS <2. g Unfit patient: creatinine clearance <60 mL/min and PS≥2. h Patients experience no progression after 1L chemotherapy (stable or responsive disease). Maintenance avelumab has shown a benefit in overall survival (pending availability of the molecule).
Fig 2
Fig 2. Schematic diagram of model utilized in the cost-effectiveness analysis.
BSC, best supportive care; IO, immuno-oncotherapy; Tx, treatment.
Fig 3
Fig 3. Area under the curve model developed for the cost-effectiveness analysis.
OS, overall survival; PPS, post-progression survival; PFS, progression-free survival.
Fig 4
Fig 4. OS KM curves followed by log-normal extrapolation beyond KM curves for both arms (reference analysis).
1LM, first-line maintenance; BSC, best supportive care; KM, Kaplan-Meier; OS, overall survival.
Fig 5
Fig 5. PFS KM curves followed by Weibull and log-normal extrapolations for avelumab plus BSC and BSC alone, respectively (reference analysis).
1LM, first-line maintenance; BSC, best supportive care; KM, Kaplan-Meier; PFS, progression-free survival.
Fig 6
Fig 6. TTD KM curves followed by generalized gamma and log-logistic extrapolations for avelumab plus BSC and BSC alone, respectively (reference analysis).
1LM, first-line maintenance; BSC, best supportive care; KM, Kaplan-Meier; TTD, time to treatment discontinuation.
Fig 7
Fig 7. Tornado diagram for the one-way sensitivity analysis.
1LM, first-line maintenance, AE, adverse event; BSC, best supportive care; ICER, incremental cost-effectiveness ratio; IO, immuno-oncotherapy; KM, Kaplan-Meier; OS, overall survival; pop2, population 2; QALY, quality-adjusted life-year; sub, subsequent; TTD, time to treatment discontinuation; Tx, treatment.
Fig 8
Fig 8. Scatterplot of the probabilistic sensitivity analysis comparing avelumab plus BSC versus BSC alone.
BSC, best supportive care.
Fig 9
Fig 9. Acceptability curve of cost-effectiveness for the reference analysis.
1LM, first-line maintenance; BSC, best supportive care.
See this image and copyright information in PMC

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