Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical trial evidence shows that tucatinib combination significantly increases the time before cancer progression and overall survival compared to trastuzumab with capecitabine, with a median progression-free survival of 7.8 months versus 5.6 months and overall survival of 21.9 months versus 17.4 months. However, the comparison with trastuzumab with capecitabine does not reflect standard Healthcare practice, which limits the strength of the evidence.
Cost effectiveness
The economic model indicates that tucatinib combination is likely to be cost-effective, with estimates suggesting it falls within NICE’s acceptable range for Healthcare resources. The committee acknowledged that the model does not capture all benefits, particularly for patients with brain metastases, which could further support its cost-effectiveness.
Quality of life
The evidence suggests that tucatinib combination likely improves quality of life for patients with HER2-positive breast cancer, particularly for those with brain metastases. The clinical experts indicated that the treatment could enhance quality of life before and after cancer progression, although the exact utility values used in the economic model were uncertain.
Supporting Domains
Safety and Adverse Effects
Tucatinib has a good safety profile, with manageable adverse effects reported in clinical trials. The clinical experts noted that the treatment is well-tolerated, and the adverse events are mostly mild to moderate, which supports its use in the patient population.
Comparator Selection
The relevant comparators identified include capecitabine, vinorelbine, and eribulin, which are appropriate for the patient population. However, the initial use of trastuzumab with capecitabine as a comparator was deemed inappropriate as it is not standard care in the Healthcare, which raises concerns about the robustness of the evidence.
Patient Population and Subgroups
The HER2CLIMB trial population is considered representative of the UK clinical practice, including a significant proportion of patients with brain metastases. This enhances the generalizability of the findings to the intended patient population.
Care Pathway Integration
Tucatinib can be integrated into existing treatment pathways with minor adjustments, as it is administered alongside trastuzumab and capecitabine, which are already part of the treatment regimen for HER2-positive breast cancer.
Resource Use and Cost Implications
The budget impact of tucatinib combination is manageable, and the committee noted that the treatment is likely to provide good value for the Healthcare, especially considering the potential benefits for patients with brain metastases.
Evidence Quality and Robustness
The evidence base is supported by a well-conducted Phase III trial (HER2CLIMB) with low bias risk. However, some methodological concerns were raised regarding the indirect treatment comparisons, which could affect the robustness of the conclusions.
Uncertainty, Sensitivity, and Broader Impacts
While there are uncertainties related to the indirect treatment comparisons and the utility values used, the overall context of unmet need and the potential benefits of tucatinib combination mitigate some of these concerns.
