Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The evidence for crizotinib indicates that it has comparable efficacy to entrectinib, which is the standard treatment for ROS1-positive advanced non-small-cell lung cancer. However, there is no direct trial data comparing crizotinib to entrectinib, and the evidence is primarily based on indirect comparisons. This limits the strength of the claim for superiority, thus justifying a B++ rating.
Cost effectiveness
Crizotinib is suggested to have lower or similar costs compared to entrectinib, which supports its recommendation based on cost-effectiveness. The presence of a commercial arrangement further enhances its cost-effectiveness profile, justifying an A+ rating.
Quality of life
The document does not provide any data or discussion regarding the impact of crizotinib on health-related quality of life, making it impossible to assess this factor.
Supporting Domains
Safety and Adverse Effects
While the document does not detail specific adverse effects, crizotinib is generally considered to have an acceptable safety profile. The absence of significant safety concerns in the context of its use supports a rating of A.
Comparator Selection
The comparator, entrectinib, is appropriate as it is the usual treatment for the same patient population. However, the lack of direct head-to-head trial data limits the robustness of the comparison, leading to a B++ rating.
Patient Population and Subgroups
The patient population for crizotinib is well-defined as adults with ROS1-positive advanced non-small-cell lung cancer. The guidance indicates that the treatment is recommended for those who have not previously received ROS1 inhibitors, which supports a moderate level of representativeness.
Care Pathway Integration
Crizotinib can be integrated into existing treatment pathways with minimal disruption, as it is recommended alongside entrectinib, which is already in use. This suggests that only minor adjustments are needed for its implementation.
Resource Use and Cost Implications
The document indicates that crizotinib has a cost profile that is either lower or similar to that of entrectinib, suggesting a manageable budget impact. This supports a rating of A for resource use and cost implications.
Evidence Quality and Robustness
The evidence base for crizotinib includes indirect comparisons but lacks direct Phase III trial data. This results in moderate concerns regarding the robustness of the evidence, justifying a B++ rating.
Uncertainty, Sensitivity, and Broader Impacts
The guidance indicates that crizotinib addresses a significant unmet need in the treatment of ROS1-positive advanced non-small-cell lung cancer, which helps mitigate some uncertainties. However, the lack of direct comparative data introduces some residual uncertainty.
