Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Regorafenib shows moderate benefit over current care, with clinical trial results indicating an increase in overall survival compared to best supportive care. The pooled hazard ratio from the CORRECT and CONCUR trials suggests a significant improvement in survival, although the lack of direct comparison with trifluridine-tipiracil introduces some uncertainty.
Cost effectiveness
The cost-effectiveness estimates for regorafenib are within acceptable thresholds for Healthcare resources, particularly when considering the commercial arrangement that provides a discount. The ICER is defensible under common thresholds, indicating a strong economic value.
Quality of life
The evidence indicates minimal or mixed impact on quality of life, with no significant differences reported between regorafenib and best supportive care. The utility values derived from the trials suggest that while regorafenib may not worsen HRQoL, it does not provide substantial improvements either.
Supporting Domains
Safety and Adverse Effects
Regorafenib has an acceptable safety profile, with adverse events being manageable. The comparison of adverse events with trifluridine-tipiracil shows that while regorafenib has a higher likelihood of treatment-emergent adverse events, these are generally mild to moderate and can be managed effectively.
Comparator Selection
The committee noted that while regorafenib was compared to best supportive care, the lack of direct head-to-head trials with trifluridine-tipiracil limits the robustness of the comparator selection. The indirect treatment comparison suggests similar effectiveness, but this introduces uncertainty.
Patient Population and Subgroups
The trials included diverse populations, and while there are some concerns regarding representativeness, the core population reflects those typically seen in clinical practice. The committee acknowledged that the trials were not adequately powered for subgroup analyses, but the overall population is considered relevant.
Care Pathway Integration
Regorafenib can be integrated into existing treatment pathways with minor adjustments, as it is administered orally and can be taken at home. This aligns well with current clinical practices for managing metastatic colorectal cancer.
Resource Use and Cost Implications
The budget impact of regorafenib is manageable, and the economic model suggests that the resource implications are justifiable given the expected health outcomes. The committee concluded that the treatment is resource-efficient.
Evidence Quality and Robustness
The evidence base is supported by two Phase 3 RCTs, although there are some methodological concerns and biases noted. The overall quality of evidence is acceptable, with a low risk of bias in the primary studies.
Uncertainty, Sensitivity, and Broader Impacts
There are notable uncertainties regarding the indirect treatment comparisons and the generalizability of trial results to the broader population. The committee recognized these uncertainties but deemed them manageable within the context of the decision-making process.
