Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The evidence from the JAVELIN trial indicates that avelumab shows promising efficacy outcomes, particularly in second-line treatment, with an objective response rate of 33% at 18 months. However, the trial was a single-arm study with no direct comparison to chemotherapy, leading to significant uncertainty regarding its effectiveness. The committee noted that the overall survival data were still immature, and thus the results should be interpreted with caution.
Cost effectiveness
The ICER for avelumab compared to best supportive care was reported at £37,846 per QALY gained, which is within the acceptable range for end-of-life treatments. However, the committee expressed concerns about the uncertainty surrounding the estimates, particularly due to the limited data and assumptions made in the economic model.
Quality of life
The company collected health-related quality-of-life data using validated tools (EQ-5D-5L and FACT-M). Although the baseline utilities were considered high, the committee accepted them as they were consistently applied across treatment groups. The potential for improved quality of life compared to chemotherapy was acknowledged, indicating moderate gains.
Supporting Domains
Safety and Adverse Effects
Avelumab was noted to have a generally acceptable tolerability profile, with no treatment-related deaths reported in the JAVELIN trial. Although treatment-related adverse event rates were high, the committee concluded that avelumab is better tolerated than chemotherapy, indicating a very good safety profile.
Comparator Selection
The appropriate comparators were identified as chemotherapy for first-line treatment and best supportive care for second-line treatment. However, the lack of direct comparisons in the JAVELIN trial raises concerns about the robustness of the evidence, leading to a B++ rating.
Patient Population and Subgroups
The trial population was somewhat representative, but there were notable exclusions, such as immunosuppressed patients. The committee highlighted concerns regarding the generalizability of the results to the broader patient population, particularly in the UK context.
Care Pathway Integration
Avelumab can be integrated into existing care pathways with minor adjustments. The committee noted that it fits well within the current treatment landscape for metastatic Merkel cell carcinoma, requiring no significant changes to infrastructure.
Resource Use and Cost Implications
The economic model indicated a manageable budget impact, but the committee expressed concerns about the high resource burden associated with treatment, particularly given the uncertainties in the ICER estimates. This led to a B++ rating.
Evidence Quality and Robustness
The evidence base is primarily derived from a single-arm trial, which raises concerns about bias and the robustness of the findings. The committee noted the need for further data collection to strengthen the evidence base, resulting in a B+ rating.
Uncertainty, Sensitivity, and Broader Impacts
There is significant uncertainty surrounding the clinical and cost-effectiveness estimates due to the limited data and assumptions made in the economic model. The committee acknowledged the potential for broader impacts but rated this factor as B+ due to the high uncertainty.
