Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical evidence for trastuzumab deruxtecan is based on the single-arm DESTINY-Breast01 trial, which shows promising efficacy with an overall response rate of 61.4%. However, the lack of direct comparisons with standard treatments and the immaturity of the overall survival data introduce significant uncertainty. The committee noted that while indirect comparisons suggest potential benefits, the evidence does not demonstrate a clear superiority over existing therapies.
Cost effectiveness
The ICER for trastuzumab deruxtecan is estimated at £47,230 per QALY gained, which is plausible but highly uncertain due to the immaturity of the overall survival data and reliance on indirect comparisons. The committee concluded that the cost-effectiveness estimates are not robust enough to support routine use without further evidence.
Quality of life
Health-related quality of life data were not collected in the DESTINY-Breast01 trial, and the company used utility values from other NICE appraisals. While the approach is broadly appropriate, the absence of direct HRQoL data from the trial raises concerns about the robustness of the findings.
Supporting Domains
Safety and Adverse Effects
Trastuzumab deruxtecan has an acceptable safety profile, although it is associated with a relatively high rate of interstitial lung disease (ILD). Clinical experts indicated that ILD can be managed effectively, and the adverse effects are generally less severe compared to traditional chemotherapies, which supports its tolerability.
Comparator Selection
The evidence primarily comes from a single-arm trial, and while indirect comparisons were made with standard treatments like capecitabine, vinorelbine, and eribulin, the limitations of these comparisons and the lack of direct evidence weaken the robustness of the findings.
Patient Population and Subgroups
The DESTINY-Breast01 trial population is broadly representative of the intended patient population in the Healthcare, with most participants having multiple prior treatments. The committee noted that the trial’s characteristics align well with the clinical context, enhancing generalizability.
Care Pathway Integration
Trastuzumab deruxtecan can be integrated into existing treatment pathways for HER2-positive breast cancer, requiring minimal adjustments. The committee noted that it would replace existing therapies, which facilitates its adoption in clinical practice.
Resource Use and Cost Implications
While trastuzumab deruxtecan has the potential for cost-effectiveness, the high cost and uncertainty surrounding its economic impact raise concerns. The committee highlighted that the budget impact could be significant, necessitating careful consideration of resource allocation.
Evidence Quality and Robustness
The evidence base is primarily derived from a single-arm trial with immature data, leading to significant uncertainty. While the trial design is acceptable, the lack of robust comparative evidence and potential biases limit the overall reliability of the findings.
Uncertainty, Sensitivity, and Broader Impacts
There is considerable uncertainty regarding the long-term outcomes and cost-effectiveness of trastuzumab deruxtecan. The committee noted that while the treatment addresses an unmet need, the high degree of uncertainty surrounding its clinical benefits and economic implications could restrict its use.
