Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical evidence from the INVICTUS trial indicates that ripretinib plus best supportive care significantly improves overall survival and progression-free survival compared to placebo plus best supportive care, with hazard ratios of 0.41 and 0.16 respectively. However, the committee noted that the clinical effectiveness is somewhat limited by the uncertainty regarding the treatment effect in the Healthcare context, particularly due to the stopping rule not reflecting clinical practice.
Cost effectiveness
Quality of life
The utility values used in the economic model were deemed uncertain, with the committee expressing concerns about the appropriateness of the values derived from the INVICTUS trial. The ERG suggested alternative utility values from the GRID trial, indicating a lack of consensus on the impact of ripretinib on HRQoL.
Supporting Domains
Safety and Adverse Effects
Ripretinib was noted to have a manageable safety profile compared to other tyrosine kinase inhibitors, with patient experts indicating that its side effects are more manageable than those of imatinib and regorafenib. The committee acknowledged the adverse effects but considered them acceptable given the context of treatment options.
Comparator Selection
Best supportive care was selected as the primary comparator, which is appropriate given the treatment landscape. However, the committee noted that continued regorafenib after progression could also be a relevant comparator, indicating some limitations in the comparator selection.
Patient Population and Subgroups
The trial population in the INVICTUS study included patients who had received three or more prior treatments, which is representative of the intended patient population. However, there were concerns regarding the generalizability of the results to the Healthcare population, particularly regarding the number of previous treatments.
Care Pathway Integration
The integration of ripretinib into existing care pathways may require significant adjustments, particularly due to the stopping rule that does not align with clinical practice. The committee noted that the economic model did not reflect expected clinical practice, which raises concerns about integration.
Resource Use and Cost Implications
The economic model’s assumptions and the stopping rule led to a high resource burden and uncertainty regarding the budget impact. The committee concluded that the model did not provide a plausible estimate of costs associated with ripretinib, indicating potential unsustainability.
Evidence Quality and Robustness
While the INVICTUS trial provides robust evidence, the committee identified significant limitations in the economic modeling and the assumptions made regarding treatment discontinuation and overall survival. This raises concerns about the robustness of the evidence base.
Uncertainty, Sensitivity, and Broader Impacts
There is considerable uncertainty surrounding the cost-effectiveness of ripretinib, particularly due to the stopping rule and the assumptions made in the economic model. The committee noted that these uncertainties could restrict the use of ripretinib in practice.
