Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical trial evidence indicates that cemiplimab plus chemotherapy shows comparable efficacy to existing options, specifically placebo plus chemotherapy, but lacks direct comparison with pembrolizumab plus chemotherapy. The trial was stopped early due to superior overall survival, which raises concerns about potential overestimation of treatment effects. The indirect comparisons presented show uncertainty, particularly in overall survival outcomes, leading to a rating of B++.
Cost effectiveness
The cost-effectiveness estimates for cemiplimab plus chemotherapy are above the acceptable ICER threshold of £20,000 per QALY gained, with significant uncertainties in the economic model. The committee concluded that the evidence does not support that cemiplimab represents a cost-effective use of NHS resources, resulting in a rating of C.
Quality of life
While the committee acknowledged that advanced NSCLC can significantly affect health-related quality of life, there is insufficient evidence presented regarding the specific impact of cemiplimab on HRQoL compared to standard care. The absence of robust patient-reported outcomes or validated tools to measure HRQoL improvements leads to a rating of B+.
Supporting Domains
Safety and Adverse Effects
Cemiplimab plus chemotherapy has an acceptable safety profile, with adverse events primarily attributed to the chemotherapy component. The evidence suggests manageable adverse effects, leading to a rating of A.
Comparator Selection
The company selected pembrolizumab plus chemotherapy as the sole comparator, which is appropriate for the specified target population. However, the lack of direct head-to-head trials with this comparator raises concerns about the robustness of the evidence, leading to a rating of B++.
Patient Population and Subgroups
The trial population is broadly representative of the intended patient population with advanced NSCLC, and the committee concluded that the target population could be identified by healthcare professionals. This leads to a rating of A.
Care Pathway Integration
Cemiplimab can be integrated into existing treatment pathways with minor adjustments, as it aligns with current clinical practices for advanced NSCLC. This results in a rating of A+.
Resource Use and Cost Implications
The resource implications of implementing cemiplimab are significant, particularly given the high cost and the uncertainties in the economic model. This leads to a rating of B.
Evidence Quality and Robustness
The evidence base includes a phase 3 trial, but there are notable uncertainties and biases, particularly regarding indirect comparisons and the early termination of the trial. This results in a rating of B++.
Uncertainty, Sensitivity, and Broader Impacts
There are significant uncertainties regarding the cost-effectiveness and clinical effectiveness of cemiplimab, particularly in relation to the indirect comparisons with pembrolizumab. This leads to a rating of B+.
