Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Zolbetuximab plus chemotherapy shows a moderate benefit over standard care, with statistically significant improvements in progression-free survival (PFS) and overall survival (OS) compared to placebo plus chemotherapy in the SPOTLIGHT and GLOW trials. However, it has not been directly compared to nivolumab or pembrolizumab, which limits the strength of the evidence.
Cost effectiveness
The cost-effectiveness estimates for zolbetuximab plus chemotherapy are above what NICE considers acceptable for Healthcare resources. Although it is less costly than some comparators, it may also be less effective, leading to concerns about its overall value.
Quality of life
While the document mentions the impact of the condition on quality of life, it does not provide specific data on HRQoL improvements associated with zolbetuximab. The evidence suggests that the treatment may have manageable side effects, but there is insufficient data to demonstrate significant improvements in quality of life.
Supporting Domains
Safety and Adverse Effects
Zolbetuximab has a very good safety profile with manageable adverse events, primarily nausea and vomiting, which are less severe compared to those associated with immunotherapies. The evidence indicates that adverse events are mostly mild to moderate.
Comparator Selection
The treatment has not been directly compared with nivolumab or pembrolizumab, which are relevant comparators for the patient population. The indirect comparisons used have significant uncertainty, which raises concerns about the robustness of the evidence.
Patient Population and Subgroups
The trials included a representative population of adults with untreated claudin-18.2-positive, HER2-negative gastric or gastro-oesophageal junction adenocarcinoma. However, there are some limitations regarding the generalizability to all subgroups, particularly those eligible for immunotherapy.
Care Pathway Integration
Zolbetuximab can be integrated into existing treatment pathways with minor adjustments, as it is used in combination with standard chemotherapy regimens. The document indicates that it does not require significant changes to current clinical practice.
Resource Use and Cost Implications
The economic model indicates a notable cost burden associated with zolbetuximab, particularly due to its acquisition costs and the need for testing. This raises concerns about its affordability within the Healthcare.
Evidence Quality and Robustness
The pivotal trials SPOTLIGHT and GLOW are large, phase 3 randomized controlled trials that provide robust evidence for the efficacy of zolbetuximab. However, the reliance on indirect comparisons introduces some uncertainty.
Uncertainty, Sensitivity, and Broader Impacts
There is considerable uncertainty regarding the indirect comparisons with immunotherapies, which may affect the overall conclusions about zolbetuximab’s effectiveness. The committee noted the need for further evidence to clarify these uncertainties.
