Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Abemaciclib plus fulvestrant has shown moderate benefit in improving progression-free survival compared to placebo plus fulvestrant, with a median progression-free survival of 16.87 months versus 9.27 months. However, the improvement in overall survival is less certain, as it was not statistically significant in the post-amendment group. This indicates a moderate therapeutic impact, but the uncertainty around overall survival limits the rating.
Cost effectiveness
The cost-effectiveness estimates for abemaciclib plus fulvestrant are considered plausible and fall within the range that NICE deems acceptable for Healthcare resources. Although there is some uncertainty regarding the ICER, the treatment is likely to be cost-effective, especially given the need for alternatives to existing therapies.
Quality of life
The treatment is valued by patients as it can delay the need for chemotherapy, which is associated with significant side effects that negatively impact quality of life. Patient and clinical expert feedback indicates that the option of a CDK4/6 inhibitor is preferred due to its potential to manage side effects better than the comparator, exemestane plus everolimus.
Supporting Domains
Safety and Adverse Effects
Abemaciclib plus fulvestrant has an acceptable safety profile, with manageable adverse effects such as diarrhea. While there are notable side effects, they are generally considered preferable to those associated with chemotherapy, indicating a good tolerability overall.
Comparator Selection
The treatment was compared indirectly with exemestane plus everolimus, which is the standard of care. However, the lack of direct head-to-head trials introduces some limitations in the robustness of the evidence regarding comparative effectiveness.
Patient Population and Subgroups
The trial population is broadly representative of the intended patient population, with specific subgroup analyses conducted. The inclusion of patients who had progressed on prior endocrine therapy aligns well with the target demographic for this treatment.
Care Pathway Integration
Abemaciclib plus fulvestrant can be integrated into existing treatment pathways with minor adjustments. The treatment does not require significant changes to current clinical practices, making it a feasible option for healthcare providers.
Resource Use and Cost Implications
The treatment is expected to have a manageable budget impact, especially considering the patient access scheme that provides a discount. This makes it a viable option for the Healthcare without imposing an unsustainable financial burden.
Evidence Quality and Robustness
The evidence base is supported by a robust Phase 3 trial (MONARCH 2) with a well-defined methodology. Although there are some concerns regarding the protocol amendment, the overall quality of evidence remains strong.
Uncertainty, Sensitivity, and Broader Impacts
While there are uncertainties regarding the clinical effectiveness estimates, particularly in overall survival, the treatment addresses a significant unmet need in the patient population. The context of its use in managing advanced breast cancer adds to its favorable assessment.
