The cost–effectiveness of zolbetuximab in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma

Abstract

Aim: To estimate the cost–effectiveness of zolbetuximab plus capecitabine/oxaliplatin (CAPOX) in CLDN18.2-positive, HER2-negative, mG/GEJ adenocarcinoma from the perspective of Chinese payers. Materials & methods: A partitioned survival model was developed to assess the costs, quality-adjusted life years (QALYs) and incremental cost–effectiveness ratios (ICER) of zolbetuximab plus CAPOX versus placebo plus CAPOX. Sensitivity analyses were performed to test the robustness of model. Results: Zolbetuximab plus CAPOX gained an additional cost of $91,551 and an extra health benefit of 0.24 QALY over placebo plus CAPOX, producing an ICER of $388,186/QALY, which exceeded the willingness-to-pay threshold of $38,223/QALY. Sensitivity analysis shows that the model was generally robust. Conclusion: Zolbetuximab plus CAPOX would not be a cost-effective first-line treatment regimen in CLDN18.2-positive, HER2-negative, mG/GEJ adenocarcinoma in China.

Summary points

Aim

• Zolbetuximab, a new drug firstly targeting CLDN18.2 protein, presents remarkable efficacy in CLDN18.2-positive, HER2-negative, metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma, but it might increase disease burden due to its' high acquisition price.

• The study aimed to evaluate the cost–effectiveness of zolbetuximab plus capecitabine/oxaliplatin (CAPOX) in CLDN18.2-positive, HER2-negative, mG/GEJ adenocarcinoma from the perspective of Chinese payers and the result would provide a scientific foundation for reasonable pricing of zolbetuximab.

Materials & methods

• A three-state partitioned survival model was established to compare the survival benefits and treatment costs of two strategies: zolbetuximab plus CAPOX vs placebo plus CAPOX.

• Efficacy data was obtained from the clinical trial (GLOW, NCT03653507). Eight survival functions were utilized to fit survival curves and extrapolate clinical outcomes over 5-year treatment. The prices of drugs were derived from Chinese official website except that of zolbetuximab, whose price was obtained by referencing a similar novel drug. Costs of disease management and serious adverse events treatment were extracted from published articles. Utility values were gained from published literature.

• The primary outputs were costs, quality-adjusted life-years (QALYs) and incremental cost–effectiveness ratio (ICER). The willingness-to-pay (WTP) threshold was set as $38,223/QALY, which is three-times the per capita gross domestic product of China in 2022. One-way sensitivity analysis, probabilistic sensitivity analysis (PSA), price simulation and subgroup analyses were performed.

Results

• Zolbetuximab plus CAPOX was projected to gain an additional cost of $91,551 and an extra health benefits of 0.24 QALY over placebo plus CAPOX, producing an ICER of $388,186/QALY, which was far beyond the WTP threshold of $38,223/QALY.

• One-way sensitivity analysis manifested that the utility value in progression-free survival, body surface area and the cost of zolbetuximab had the greatest influence on results. The probability of zolbetuximab being cost-effective was 0 in PSA.

• Price simulation results indicated that zolbetuximab would be economical at a price below $0.2522/mg.

• Subgroup analyses found that zolbetuximab plus CAPOX was associated with favorable cost-effective outcomes in several subgroups, including patients under 65 years old, patients from Asia, and those whose cancer primarily sites in the stomach.

Conclusion

• Zolbetuximab plus CAPOX would not be a cost-effective first-line treatment regimen in CLDN18.2-positive, HER2-negative, mG/GEJ adenocarcinoma from the Chinese payers' perspective.

• Setting the benchmark price of zolbetuximab as $0.2522/mg could reverse the conclusion. Our evidence-based pricing strategy can provide information for decision-makers to tailor treatment options for particular patients or set reasonable drug price.

Keywords: :

• CLDN18.2 protein
• cost–effectiveness
• gastric or gastroesophageal junction adenocarcinoma
• value-based pricing
• zolbetuximab

Author contributions

S Lai: conceptualization, writing-original draft preparation; S Luo: methodology, software; Q Huang, S Lin: data curation; X Huang, H Xue, Y Cai, X Xu: validation; X Weng: conceptualization, writing-reviewing and editing.

Financial disclosure

The Joint Funds for the Innovation of Science and Technology, Fujian Province(2020Y9132). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Data availability statement

All data generated or analyzed during this study are included in this article and the supplementary material.

Acknowledgments

We would like to thank the GLOW trial for providing the raw data.

Additional information

Funding

The Joint Funds for the Innovation of Science and Technology, Fujian Province (2020Y9132).