Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical evidence for selinexor plus dexamethasone is derived from the STORM trial, a phase 2b single-arm study, which reported an overall response rate of 25.3% and a median overall survival of 8.4 months. However, there is no direct comparison with best supportive care (BSC), leading to uncertainty in the effectiveness claims. The evidence suggests comparable efficacy to existing options but lacks the robustness of Phase 3 trials, thus justifying a B++ rating.
Cost effectiveness
The ICER for selinexor plus dexamethasone is estimated at £24,009 per QALY gained, which is below NICE’s cost-effectiveness threshold. This suggests that the treatment is marginally cost-effective, especially when considering the severity of the condition and the commercial arrangement that provides a discount, justifying an A rating.
Quality of life
The document does not provide specific data on HRQoL improvements associated with selinexor plus dexamethasone. While the treatment is expected to have some positive impact on quality of life due to its novel mechanism, the absence of validated tools or significant domain-specific improvements leads to a B+ rating.
Supporting Domains
Safety and Adverse Effects
The safety profile of selinexor plus dexamethasone is acceptable, with manageable adverse events reported. The document indicates that while there are notable adverse effects, they are generally mild to moderate, supporting an A rating for safety.
Comparator Selection
The only comparator considered relevant by the committee is best supportive care (BSC), as other treatments were deemed inappropriate for the penta-refractory population. While BSC is a valid comparator, the lack of direct evidence comparing selinexor with BSC limits the robustness of the evidence, leading to a B++ rating.
Patient Population and Subgroups
The trial population in the STORM study is somewhat representative of the intended patient population, particularly in terms of ECOG performance status. Although there are some differences, the core population is adequately covered, justifying an A rating.
Care Pathway Integration
Selinexor plus dexamethasone can be integrated into existing treatment pathways with minor adjustments. The treatment is oral, which facilitates administration, and no significant new infrastructure is required, supporting an A+ rating.
Resource Use and Cost Implications
The budget impact of selinexor is manageable, particularly with the commercial arrangement in place. The treatment is expected to provide a net benefit in terms of resource use, justifying an A rating.
Evidence Quality and Robustness
The evidence base is primarily derived from a single phase 2b trial, which raises concerns about robustness and generalizability. While the evidence is acceptable, it lacks the rigor of multiple Phase III trials, leading to a B++ rating.
Uncertainty, Sensitivity, and Broader Impacts
There is significant uncertainty surrounding the cost-effectiveness estimates and overall survival projections. The committee acknowledged this uncertainty but considered the treatment’s innovative nature and the severity of the condition, leading to a B+ rating.
