Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Erdafitinib demonstrated a statistically significant improvement in overall survival (OS) and progression-free survival (PFS) compared to chemotherapy in the THOR trial. The primary endpoint of OS was 12.06 months for erdafitinib versus 7.79 months for chemotherapy, with a hazard ratio of 0.64. This indicates a clear clinical advantage, although the comparators used in the trial were not the standard of care in Healthcare practice.
Cost effectiveness
The incremental cost-effectiveness ratio (ICER) for erdafitinib was determined to be around £28,182, which is within the acceptable range for NICE. The committee noted that the ICER was towards the upper end of what is considered cost-effective, especially given the high unmet need in this patient population.
Quality of life
The THOR trial collected health-related quality-of-life data, and the utility values derived from the multivariable regression model were considered more appropriate for decision making. While the exact values are confidential, the committee concluded that the treatment would likely improve HRQoL for patients suffering from a debilitating condition.
Supporting Domains
Safety and Adverse Effects
Erdafitinib was associated with a favorable safety profile, with adverse events primarily being manageable and mild to moderate. The committee noted that the treatment’s toxicity profile was more favorable compared to traditional chemotherapy options, which often require frequent hospital visits.
Comparator Selection
While erdafitinib was not directly compared to the standard of care (paclitaxel with or without carboplatin), indirect comparisons were made. The committee acknowledged that the lack of direct comparison limits the strength of the evidence but accepted the indirect comparisons as informative.
Patient Population and Subgroups
The trial population was considered broadly representative of the intended patient population, with the committee noting that the average age and health status were aligned with those expected in Healthcare practice. However, some concerns about generalizability due to the ECOG performance status were raised.
Care Pathway Integration
Erdafitinib is an oral treatment that can be integrated into existing care pathways with minimal disruption. The committee noted that it would likely require fewer hospital visits compared to traditional chemotherapy, making it easier to adopt in clinical practice.
Resource Use and Cost Implications
The committee concluded that the resource use associated with erdafitinib would be lower due to less frequent outpatient visits compared to chemotherapy. This aligns with the overall cost-effectiveness of the treatment, which is favorable given the expected resource implications.
Evidence Quality and Robustness
The evidence base is primarily derived from a Phase 3 RCT (THOR), which is robust. However, the committee noted some limitations regarding the generalizability of the trial results to the broader Healthcare population, particularly concerning missing data and the health status of participants.
Uncertainty, Sensitivity, and Broader Impacts
While some uncertainties remain regarding the generalizability of the evidence and the cost-effectiveness estimates, the committee felt that the high unmet need and the potential benefits of erdafitinib in a poorly served patient population mitigated these concerns.
