Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Brigatinib shows moderate benefit over crizotinib, with evidence from the ALTA-1L trial indicating statistically significant improvements in progression-free survival. However, the overall survival data is uncertain due to high crossover rates and immature data, preventing a definitive conclusion of superiority over alectinib.
Cost effectiveness
The cost-effectiveness estimates for brigatinib are within acceptable thresholds for Healthcare resources, particularly when considering the confidential discount. The net monetary benefit analyses indicate that brigatinib is likely cost-effective compared to alectinib.
Quality of life
The evidence suggests that brigatinib may reduce treatment burden compared to alectinib, which requires more tablets per day. This reduction in treatment burden could positively impact HRQoL, although specific validated HRQoL data were not provided.
Supporting Domains
Safety and Adverse Effects
Brigatinib has a favorable safety profile with manageable adverse effects compared to alectinib, which has been noted to cause significant side effects. The committee recognized the reduced treatment burden and potential for better tolerability.
Comparator Selection
The appraisal committee appropriately selected alectinib as the main comparator, supported by clinical expert input. Crizotinib was also considered, but alectinib is the standard of care for this patient population.
Patient Population and Subgroups
The trial population is representative of the intended patient population with ALK-positive advanced NSCLC. However, there are some concerns regarding the generalizability of the ALESIA trial data, which was excluded from the analysis.
Care Pathway Integration
Brigatinib can be integrated into existing treatment pathways with minimal adjustments, as it offers a simpler dosing regimen compared to alectinib, which may improve adherence and patient outcomes.
Resource Use and Cost Implications
The overall resource implications of brigatinib are manageable, especially considering the potential cost savings associated with its use compared to alectinib and crizotinib, particularly in terms of treatment burden.
Evidence Quality and Robustness
The evidence base is primarily derived from the ALTA-1L trial, a Phase 3 RCT, which provides a strong foundation. However, the uncertainty in overall survival data and reliance on indirect comparisons introduces some methodological concerns.
Uncertainty, Sensitivity, and Broader Impacts
While there is some uncertainty regarding overall survival benefits, the context of unmet need and the potential for brigatinib to provide a new treatment option for patients with limited alternatives mitigates some of this uncertainty.
