Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The evidence from the CHRYSALIS trial indicates that amivantamab has a median progression-free survival of 6.74 months and a median overall survival of 22.77 months. However, the lack of direct comparative evidence and reliance on indirect treatment comparisons using real-world data introduces significant uncertainty regarding the clinical benefit compared to existing treatments. The committee noted that while the results were clinically meaningful, the absence of a robust comparator limits the strength of the evidence.
Cost effectiveness
The most plausible ICER for amivantamab is reported to be around £50,000 per QALY gained, which is above the acceptable threshold for Healthcare resources. The committee expressed concerns about the uncertainty surrounding the ICER due to the lack of direct comparative evidence and the use of a blended comparator, which raises questions about the cost-effectiveness of amivantamab.
Quality of life
The document indicates that the patient population experiences significant impacts on quality of life due to their condition. However, the evidence for HRQoL improvements specifically attributable to amivantamab is limited, as the company did not utilize robust quality-of-life data from the CHRYSALIS trial due to low response rates. This leads to a conclusion of no demonstrated benefit in HRQoL compared to standard care.
Supporting Domains
Safety and Adverse Effects
The safety profile of amivantamab appears acceptable, with adverse events reported in both the efficacy and safety populations being similar. The committee noted that the treatment is well tolerated, and the adverse events are manageable, indicating a good safety profile relative to existing therapies.
Comparator Selection
The choice of comparators was criticized, particularly the inclusion of EGFR TKIs, which are not considered standard care for this patient population. The committee concluded that the blended comparator approach increased uncertainty and did not accurately reflect the standard treatment pathway, leading to concerns about the validity of the comparative effectiveness data.
Patient Population and Subgroups
The trial population is described as having a specific mutation that is rare, and the committee acknowledged the unmet need for targeted treatments in this subgroup. The evidence suggests that the population studied is relevant to the intended use of amivantamab, although there are limitations in subgroup analyses.
Care Pathway Integration
The integration of amivantamab into existing care pathways appears feasible, with minor adjustments needed for diagnostic testing. The committee noted that the treatment could fit into current clinical practice without requiring significant changes to infrastructure or training.
Resource Use and Cost Implications
The economic model indicates a notable cost burden associated with amivantamab, particularly when considering the costs of diagnostic testing for exon 20 insertion mutations. The committee expressed concerns about the overall resource implications, suggesting that the budget impact may require restrictions.
Evidence Quality and Robustness
The evidence base is primarily derived from a single-arm trial (CHRYSALIS) and indirect treatment comparisons, which introduces uncertainty and potential biases. The committee noted that while the trial results are promising, the lack of direct comparative evidence and the methodological concerns regarding the real-world evidence limit the robustness of the findings.
Uncertainty, Sensitivity, and Broader Impacts
The committee highlighted significant uncertainties related to the cost-effectiveness estimates and the indirect treatment comparisons. While there are contextual factors such as the unmet need for targeted treatments, the overall uncertainty in the evidence base raises concerns about the viability of amivantamab in routine practice.
