Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical evidence from the AEGEAN trial indicates that durvalumab with chemotherapy significantly improves event-free survival (EFS) compared to placebo, with a hazard ratio of 0.69. However, the overall survival (OS) data remains immature and does not show a statistically significant advantage, leading to a moderate benefit classification.
Cost effectiveness
The cost-effectiveness estimates for durvalumab are within the acceptable range for Healthcare resources, suggesting it is clearly cost-effective under common thresholds. The committee concluded that the ICER was plausible and defensible.
Quality of life
While the treatment aims to reduce recurrence and improve patient outcomes, specific HRQoL data from the AEGEAN trial is limited. The committee noted that the impact on quality of life was not directly assessed, leading to a mixed impact classification.
Supporting Domains
Safety and Adverse Effects
Durvalumab has a very good safety profile with mostly mild to moderate adverse events reported. Serious adverse events are rare, indicating a favorable tolerability compared to existing therapies.
Comparator Selection
The committee identified neoadjuvant nivolumab as the most relevant comparator, and the indirect comparisons made were appropriate. The evidence supports the choice of comparator in the context of current treatment practices.
Patient Population and Subgroups
The AEGEAN trial population is considered broadly generalizable to the UK clinical practice, although some demographic differences exist. The committee noted that the trial population reflects the intended patient population well.
Care Pathway Integration
The integration of durvalumab into existing care pathways requires minor adjustments, primarily related to treatment protocols. The committee concluded that it fits well within current clinical practices.
Resource Use and Cost Implications
The budget impact of durvalumab is manageable and aligns with Healthcare planning. The committee noted that while there is a notable cost burden, it is justifiable given the expected health outcomes.
Evidence Quality and Robustness
The evidence from the AEGEAN trial is robust, being a phase 3 RCT with low bias risk. However, the reliance on immature OS data introduces some uncertainty, but overall, the evidence quality is acceptable.
Uncertainty, Sensitivity, and Broader Impacts
There are notable uncertainties regarding the long-term effectiveness and the cure assumption in the economic model. The committee acknowledged these uncertainties but deemed them manageable within the context of the appraisal.
