Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The TITAN trial demonstrated that apalutamide plus ADT significantly increases radiographic progression-free survival compared to placebo plus ADT, with a hazard ratio of 0.5. However, there is no direct evidence comparing apalutamide plus ADT with ADT alone for patients who cannot have docetaxel, which introduces uncertainty regarding its effectiveness in this subgroup.
Cost effectiveness
Apalutamide plus ADT is not cost-effective compared to docetaxel, with cost-effectiveness estimates well above the acceptable range for Healthcare resources. However, it is considered acceptable compared to ADT alone for patients who cannot have docetaxel, indicating some marginal cost-effectiveness in this specific context.
Quality of life
The mean change in EQ-5D-5L scores showed no significant difference between apalutamide plus ADT and placebo plus ADT, indicating no demonstrated improvement in quality of life. The lack of significant findings suggests that while apalutamide may be tolerated, it does not provide a clear benefit in HRQoL compared to standard care.
Supporting Domains
Safety and Adverse Effects
Apalutamide plus ADT has a well-tolerated safety profile, with manageable adverse effects such as rash and hypothyroidism. The committee concluded that these adverse effects do not significantly undermine the treatment’s overall value.
Comparator Selection
The primary comparison in the TITAN trial was against placebo plus ADT, which is appropriate. However, there is a lack of direct evidence comparing apalutamide plus ADT with docetaxel plus ADT, which limits the robustness of the evidence regarding its comparative effectiveness.
Patient Population and Subgroups
The TITAN trial population included patients with ECOG scores of 0, 1, or 2, which reflects a reasonable representation of the intended patient population. However, the exclusion of patients who cannot have docetaxel raises concerns about the generalizability of the findings to this subgroup.
Care Pathway Integration
Apalutamide can be integrated into existing treatment pathways with minimal disruption, as it is an oral treatment that requires less monitoring than docetaxel. This facilitates its adoption in clinical practice.
Resource Use and Cost Implications
While the cost of apalutamide is high, the company has provided a discount arrangement, making it more manageable within the Healthcare budget. However, the overall resource implications remain a concern due to the high costs associated with its use.
Evidence Quality and Robustness
The evidence from the TITAN trial is robust, being a phase 3 randomized controlled trial. However, the lack of direct evidence for the subgroup of patients who cannot have docetaxel introduces some limitations in the overall evidence quality.
Uncertainty, Sensitivity, and Broader Impacts
There are significant uncertainties regarding the cost-effectiveness of apalutamide for patients who cannot have docetaxel, as the evidence base for this subgroup is lacking. This uncertainty may restrict its use in practice.
