Authors' objectives: The academic technology assessment group (ATAG) reviewed a report on the additional benefits and cost-effectiveness of zolbetuximab in untreated claudin-18.2 (CLDN18.2 )-positive human epidermal growth factor receptor 2 (HER2 )-negative unresectable advanced or recurrent gastric cancer, submitted by Astellas Pharma Inc. This report summarizes the results of the review and re-analysis by the ATAG. The target population was divided into two groups: (a) patients with Programmed cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥ 5, and (b) those with PD-L1 CPS <5. The intervention for each target population was zolbetuximab with chemotherapy (CAPOX), and the comparators were nivolumab with chemotherapy (CAPOX) for target population (a) and chemotherapy (CAPOX) for target population (b). For target population (a), the manufacturer identified no randomized controlled trials (RCTs) that directly compared zolbetuximab with chemotherapy (CAPOX) with nivolumab with chemotherapy (CAPOX) via the manufacturer’s systematic review (SR). Instead, they identified literature on GLOW comparing zolbetuximab with chemotherapy (CAPOX) with placebo with chemotherapy (CAPOX) and CheckMate 649 comparing nivolumab with chemotherapy (FOLFOX or CAPOX) with chemotherapy (FOLFOX or CAPOX). Using the identified literature, the manufacturer conducted a network metaanalysis (NMA) with chemotherapy as a common comparator. The analysis showed no statistically significant differences in hazard ratios (HRs) for overall survival (OS) or progression-free survival (PFS). Given that indirect comparison data may not fully represent the target population, the manufacturer concluded that the additional benefits of zolbetuximab with CAPOX over nivolumab with CAPOX could not be determined. For target population (b), the manufacturer identified literature on GLOW. Based on statistically significant differences in OS and PFS in the PD-L1 CPS <5 subgroup, they concluded that zolbetuximab with CAPOX demonstrated additional benefits over CAPOX. The ATAG independently conducted an SR to comprehensively assess the additional benefits in both populations. Our review included zolbetuximab with chemotherapy and nivolumab with chemotherapy as interventions; chemotherapy as the comparator; and OS and PFS as outcomes. The ATAG identified literature on SPOTLIGHT, GLOW, and a pooled analysis of SPOTLIGHT and GLOW final results for zolbetuximab with chemotherapy. Additionally, the ATAG identified CheckMate 649 and ATTRACTION-4 as RCTs for nivolumab with chemotherapy. For target population (a), the ATAG performed sensitivity analyses to examine the robustness of the NMA performed by the manufacturer, assuming that treatment effects did not differ according to PD-L1 CPS status. The results obtained by the ATAG aligned with the manufacturer's findings. While acknowledging this uncertainty, the ATAG determined that zolbetuximab with CAPOX showed efficacy comparable to that of nivolumab with CAPOX. For target population (b), the ATAG concluded that the manufacturer's assessment was appropriate and that zolbetuximab with CAPOX demonstrated additional benefits over CAPOX. The ATAG examined the manufacturer's economic evaluations of both populations. The analysis employed a partitioned survival model with three mutually exclusive health states: pre-progression, postprogression, and death. We identified two major issues: (1) the revised drug prices effective on April 1, 2025, were not applied, and (2) the handling of HER2 and CLDN18.2 testing costs. In our reanalysis, we applied the revised prices and excluded testing costs from both intervention and comparator arms. For target population (a), zolbetuximab with CAPOX incurred an incremental cost of 6,371,780 yen compared with nivolumab with CAPOX. For population (b), zolbetuximab with CAPOX resulted in incremental costs of 8,350,886 yen and incremental effects of 0.47 quality-adjusted life years (QALYs), yielding an incremental cost-effectiveness ratio of 17,614,324 yen/QALY. From the perspective of the Japanese public healthcare payer, zolbetuximab and CAPOX is likely to be "equivalent or inferior in effectiveness with increased costs" for target population (a) and "≥15 million yen/QALY" for target population (b).

Project Status: Completed

URL for project: https://c2h.niph.go.jp/en/

Year Published: 2025

URL for published report: https://c2h.niph.go.jp/en/results/C2H2404.html

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Japan

Organisation Name: Center for Outcomes Research and Economic Evaluation for Health

Contact Address: 2-3-6 Minami, Wako-shi, Saitama 351-0197 Japan

Contact Name: Takeru Shiroiwa

Contact Email: t.shiroiwa@gmail.com