Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Selpercatinib shows moderate benefit over existing treatments for advanced RET fusion-positive thyroid cancer and RET-mutant medullary thyroid cancer. The evidence from the LIBRETTO-001 trial indicates improved progression-free survival (PFS) and overall survival (OS) compared to cabozantinib and best supportive care, although the data is derived from indirect comparisons and lacks direct Phase 3 evidence.
Cost effectiveness
The cost-effectiveness estimates for selpercatinib are below the acceptable threshold for Healthcare resources, with an ICER around £30,000 per QALY gained. This suggests that the therapy is marginally cost-effective, especially considering the unmet need in the target population.
Quality of life
The committee noted that existing treatments for thyroid cancer can significantly impact quality of life due to side effects. Selpercatinib is expected to improve HRQoL, as indicated by patient organization submissions highlighting the debilitating symptoms of thyroid cancer. However, specific HRQoL data from validated instruments were not robustly presented.
Supporting Domains
Safety and Adverse Effects
Selpercatinib has a very good safety profile, with mostly mild to moderate adverse events reported. The committee noted that it is generally better tolerated than existing treatments, which is a significant advantage in this patient population.
Comparator Selection
The main clinical trial did not directly compare selpercatinib with usual treatments, relying instead on indirect comparisons with cabozantinib and best supportive care. While the committee acknowledged the relevance of these comparators, the lack of direct evidence limits the robustness of the findings.
Patient Population and Subgroups
The trial population includes patients aged 12 years and older, which is appropriate given the indication. The committee recognized that the population is broadly representative of those with RET alterations, although there are some limitations in subgroup analyses.
Care Pathway Integration
Selpercatinib can be integrated into existing treatment pathways with minor adjustments. The committee noted that it fits well within the current clinical practice for treating advanced thyroid cancer.
Resource Use and Cost Implications
The budget impact of selpercatinib is manageable, with the potential for cost savings due to its effectiveness and the commercial arrangement providing a discount. This aligns with the Healthcare’s resource allocation strategies.
Evidence Quality and Robustness
While the evidence base includes data from the LIBRETTO-001 trial, the reliance on indirect comparisons and the absence of robust Phase 3 data introduce some uncertainty. The committee noted gaps in the evidence that require further exploration.
Uncertainty, Sensitivity, and Broader Impacts
The committee acknowledged some uncertainties in the economic model and indirect comparisons but considered the overall context, including the unmet need for effective treatments in this population, to be favorable for selpercatinib.
