Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical evidence from the JAVELIN Bladder 100 trial demonstrates a clear clinical advantage for avelumab over best supportive care, with a statistically significant improvement in overall survival (median 21.4 months vs. 14.3 months) and progression-free survival (median 3.7 months vs. 2.0 months). The results are compelling, particularly for patients with PD-L1-positive tumors, where the risk of death was reduced by 44%. However, the lack of significant results for PD-L1-negative tumors slightly tempers the overall effectiveness rating.
Cost effectiveness
The ICER for avelumab was reported to be substantially higher than the typical thresholds considered cost-effective, with estimates around £72,933 per QALY gained. This indicates low cost-effectiveness, requiring justification for the high ICER, especially given the uncertainties surrounding the economic model and the assumptions made.
Quality of life
The committee acknowledged that urothelial cancer significantly impacts quality of life, and avelumab is positioned to improve this by delaying disease progression and providing maintenance treatment. While specific HRQoL data were not extensively detailed, the overall context suggests moderate improvements in quality of life for patients receiving avelumab compared to best supportive care.
Supporting Domains
Safety and Adverse Effects
Avelumab has a very good safety profile, with mostly mild to moderate adverse events reported. Serious adverse events were rare, indicating that the treatment is well-tolerated compared to existing therapies. This supports a strong safety rating.
Comparator Selection
The JAVELIN Bladder 100 trial compared avelumab directly with best supportive care, which is the appropriate standard of care for this patient population. This direct comparison strengthens the evidence base and supports the relevance of the findings.
Patient Population and Subgroups
The trial population of 700 adults with locally advanced or metastatic urothelial cancer is broadly representative of the intended patient population. The inclusion of patients who had received platinum-based chemotherapy aligns with current clinical practice, although some subgroup analyses could be more comprehensive.
Care Pathway Integration
Avelumab can be integrated into existing treatment pathways with minor adjustments, as it serves as a maintenance therapy following platinum-based chemotherapy. The committee noted that no new infrastructure or extensive training would be required for its implementation.
Resource Use and Cost Implications
While the treatment is expected to have a manageable budget impact, the high ICER raises concerns about the overall resource burden on the healthcare system. The committee noted that the cost implications could be significant, especially if the treatment is used widely.
Evidence Quality and Robustness
The evidence base is robust, supported by a Phase 3 RCT (JAVELIN Bladder 100) with a large sample size and low risk of bias. The committee found the trial design and execution to be of high quality, contributing to the credibility of the findings.
Uncertainty, Sensitivity, and Broader Impacts
There are notable uncertainties regarding the economic model and the assumptions made about treatment duration and effectiveness. The committee expressed concerns about the implications of these uncertainties on the overall assessment of avelumab’s value.
