Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical evidence from the FRESCO and FRESCO-2 trials demonstrates that fruquintinib significantly improves overall survival and progression-free survival compared to placebo, with hazard ratios of 0.65 and 0.66 respectively. However, the lack of direct comparison with regorafenib or trifluridine-tipiracil alone introduces some uncertainty regarding its relative effectiveness against these comparators.
Cost effectiveness
The cost-effectiveness estimates for fruquintinib fall within the acceptable range for Healthcare resources, with an ICER that is defensible given the severity of metastatic colorectal cancer and the unmet need for effective treatments. The committee concluded that the ICER was acceptable based on the provided economic model.
Quality of life
The evidence suggests that fruquintinib does not negatively impact quality of life, and the clinical experts noted that progression-free survival and quality of life are critical outcomes for patients. However, specific HRQoL data from validated instruments is limited, which prevents a higher rating.
Supporting Domains
Safety and Adverse Effects
Fruquintinib has a favorable safety profile with mostly mild to moderate adverse events reported in clinical trials. The committee noted that it is easier to tolerate than regorafenib, which has more significant side effects, thus supporting a higher rating.
Comparator Selection
While the proposed comparators (trifluridine-tipiracil alone and regorafenib) are relevant, the lack of direct head-to-head trials with these treatments introduces some limitations in the evidence base. The committee acknowledged that fruquintinib is not expected to replace trifluridine-tipiracil with bevacizumab, which further complicates the comparator landscape.
Patient Population and Subgroups
The trials included a diverse patient population, with FRESCO-2 being a global trial that included patients from the UK. However, the committee noted some differences in treatment history and demographics between the trials, which may affect generalizability.
Care Pathway Integration
Fruquintinib can be integrated into existing treatment pathways with minimal disruption, as it is positioned for use at third line or later. The committee noted that it would be an option for patients who cannot have trifluridine-tipiracil with bevacizumab, indicating a good fit within current practices.
Resource Use and Cost Implications
The economic model indicates that fruquintinib is likely to be resource-efficient, with manageable budget impacts aligned with Healthcare planning. The committee concluded that the cost implications are justifiable given the benefits provided.
Evidence Quality and Robustness
The evidence is based on two phase 3 RCTs, which are robust, but there are some concerns regarding the pooling of data from different trials and the assumptions made in the economic model. Overall, the evidence is credible but has some methodological limitations.
Uncertainty, Sensitivity, and Broader Impacts
There are notable uncertainties in the economic model, particularly regarding the proportional hazards assumption and the generalizability of trial results. The committee expressed concerns about the robustness of the NMA results, which could impact the overall conclusions.
