Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The evidence from the LIBRETTO-001 trial indicates a moderate benefit of selpercatinib over standard treatments, with an objective response rate of 61.5% and progression-free survival of 26.15 months. However, the lack of direct comparisons with docetaxel or docetaxel plus nintedanib introduces uncertainty regarding its superiority.
Cost effectiveness
The cost-effectiveness estimates for selpercatinib are within NICE’s acceptable thresholds, suggesting it is a cost-effective option for treating RET fusion-positive advanced NSCLC, especially considering the rarity of the condition.
Quality of life
The trial data includes HRQoL outcomes, indicating positive impacts on patient well-being. However, the improvements are moderate and primarily derived from subgroup analyses, which limits the robustness of the findings.
Supporting Domains
Safety and Adverse Effects
Selpercatinib has a favorable safety profile with mostly mild to moderate adverse events reported. Serious adverse events are rare, indicating good tolerability compared to existing therapies.
Comparator Selection
The comparators selected (docetaxel and docetaxel plus nintedanib) are appropriate, but the absence of direct head-to-head trials limits the strength of the evidence. Indirect comparisons introduce additional uncertainty.
Patient Population and Subgroups
The trial population is representative of the intended patient population with RET fusion-positive NSCLC, and subgroup analyses were conducted, although some gaps remain.
Care Pathway Integration
Selpercatinib can be integrated into existing treatment pathways with minimal disruption, as it is an oral therapy that does not require significant changes to current practices.
Resource Use and Cost Implications
The resource implications of selpercatinib are manageable, and the economic model suggests that it will not impose a significant burden on healthcare resources, aligning with NICE’s expectations.
Evidence Quality and Robustness
The evidence base is primarily derived from the LIBRETTO-001 trial, which is a well-designed study. However, the reliance on indirect comparisons introduces some methodological concerns.
Uncertainty, Sensitivity, and Broader Impacts
There is notable uncertainty surrounding the indirect comparisons and the long-term outcomes of selpercatinib, which may affect its broader applicability and acceptance.
