Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Cabozantinib has demonstrated clinical effectiveness compared to placebo in the CELESTIAL trial, showing a median overall survival of 10.2 months versus 8.0 months for placebo. However, there is no direct comparison with regorafenib, the relevant comparator, leading to uncertainty about its relative efficacy. The indirect comparisons suggest similar effectiveness, but the lack of direct evidence limits the strength of the conclusion.
Cost effectiveness
The cost-effectiveness estimates for cabozantinib are within the range that NICE considers acceptable, particularly given the limited treatment options for patients who have previously been treated with sorafenib. The committee concluded that cabozantinib represents a cost-effective use of Healthcare resources, especially when considering the commercial discount provided.
Quality of life
The evidence regarding HRQoL is mixed. The CELESTIAL trial indicated a potentially meaningful difference favoring placebo in HRQoL, while the RESORCE trial did not show significant differences between regorafenib and placebo. This uncertainty suggests that cabozantinib may not provide a clear benefit in HRQoL compared to existing treatments.
Supporting Domains
Safety and Adverse Effects
Cabozantinib has an acceptable safety profile, with adverse events that are manageable. The committee noted that while there are some concerns regarding its toxicity compared to regorafenib, the overall tolerability is considered acceptable, with no severe safety issues reported that would undermine its use.
Comparator Selection
The relevant comparator for cabozantinib is regorafenib, which is used in similar patient populations. However, the lack of direct head-to-head evidence means that the conclusions drawn from indirect comparisons carry limitations, leading to a rating of B++.
Patient Population and Subgroups
The patient population for cabozantinib is well-defined, focusing on adults with advanced HCC who have previously been treated with sorafenib. The inclusion criteria ensure that the trial population is representative of the intended use, although there are some limitations regarding more severe liver disease.
Care Pathway Integration
Cabozantinib can be integrated into existing treatment pathways with minor adjustments. The committee noted that it fits well within the current treatment landscape for advanced HCC, requiring no significant changes to existing clinical practices.
Resource Use and Cost Implications
The resource implications of cabozantinib are manageable, particularly with the commercial arrangement in place. The committee acknowledged that while there may be some additional monitoring costs, these are not expected to be prohibitive, supporting a rating of A.
Evidence Quality and Robustness
The evidence base for cabozantinib is primarily derived from the CELESTIAL trial, which is a well-designed RCT. However, the reliance on indirect comparisons introduces some uncertainty, leading to a rating of A rather than higher.
Uncertainty, Sensitivity, and Broader Impacts
While there are uncertainties regarding the indirect comparisons and the cost-effectiveness estimates, the overall context of limited treatment options for advanced HCC patients mitigates some of these concerns. The committee found the societal context supportive of cabozantinib’s use.
