Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The evidence from the LIBRETTO-001 trial suggests that selpercatinib could be clinically effective for untreated RET fusion-positive advanced NSCLC, with an objective response rate of 84% and a median progression-free survival of 22 months. However, the results are uncertain due to the trial’s ongoing nature and the lack of direct comparisons with standard treatments, which limits the robustness of the evidence.
Cost effectiveness
The cost-effectiveness estimates for selpercatinib are uncertain and likely higher than what NICE considers cost-effective. The committee noted that while selpercatinib could be cost-effective with more evidence, the current estimates do not support routine use without further data.
Quality of life
The clinical experts indicated that targeted treatments like selpercatinib are associated with higher quality of life compared to systemic chemotherapy. This suggests a moderate improvement in HRQoL, although specific validated tools were not mentioned in the document.
Supporting Domains
Safety and Adverse Effects
Selpercatinib has a very good safety profile with mostly mild or moderate adverse events. The clinical experts noted that it is better tolerated than current systemic chemotherapy options, which supports a strong tolerability rating.
Comparator Selection
The comparators selected for the evaluation were aligned with current Healthcare practice and included relevant standard treatments for RET fusion-positive advanced NSCLC, which supports a strong rating for comparator selection.
Patient Population and Subgroups
The trial population is considered broadly representative of the intended patient population, although there are some concerns regarding the inclusion of squamous NSCLC patients. Overall, the core population is well covered.
Care Pathway Integration
Selpercatinib can be integrated into existing treatment pathways with minor adjustments, as it is an oral medication that can be taken at home, which is a significant advantage over intravenous treatments.
Resource Use and Cost Implications
The resource implications of selpercatinib are notable, particularly due to the costs associated with genetic testing for RET fusion status and the overall treatment costs. The committee expressed concerns about the high resource burden.
Evidence Quality and Robustness
The evidence base is primarily derived from a single-arm trial, which introduces uncertainty. While there are ongoing studies that may provide additional data, the current evidence has gaps and biases that require further validation.
Uncertainty, Sensitivity, and Broader Impacts
There are significant uncertainties regarding the long-term effectiveness and cost-effectiveness of selpercatinib, particularly due to the immaturity of the trial data and the reliance on indirect comparisons. This raises concerns about its broader impacts.
