Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical evidence for pemigatinib is derived from a single-arm, non-randomised study (FIGHT-202), which does not provide direct comparative evidence against standard treatments. While the evidence suggests pemigatinib may be more effective than current treatments, the lack of direct comparison limits the robustness of this conclusion. The committee acknowledged the rarity of the cancer, which complicates the collection of robust comparative data, leading to an acceptable level of uncertainty.
Cost effectiveness
The cost-effectiveness estimates for pemigatinib are reported to be below the £50,000 per QALY threshold, with the company’s base-case ICERs being £42,076 per QALY gained compared to mFOLFOX+ASC and £45,029 per QALY gained compared to ASC alone. This indicates that pemigatinib is likely to be a cost-effective use of Healthcare resources, despite some uncertainty in the estimates.
Quality of life
The committee noted that pemigatinib has the potential to improve debilitating symptoms and health-related quality of life for patients with advanced cholangiocarcinoma. Although specific HRQoL data were not extensively detailed, the emphasis on symptom control and the potential for life extension suggest a moderate benefit in quality of life.
Supporting Domains
Safety and Adverse Effects
The safety profile of pemigatinib appears acceptable, with the committee noting that adverse events were reported from the FIGHT-202 study. While there is a lack of direct comparative safety data, the adverse events reported were manageable, and the committee concluded that the absence of significant safety concerns supports its use.
Comparator Selection
The comparators selected for the appraisal (mFOLFOX+ASC and ASC alone) are appropriate based on current clinical practice. However, the committee noted that there is uncertainty regarding the use of other chemotherapy agents in routine practice, which introduces some limitations in the comparative analysis.
Patient Population and Subgroups
The population in cohort A of the FIGHT-202 study is considered appropriate for decision-making, as it reflects the intended patient population with FGFR2 fusion or rearrangement. The committee acknowledged that while 98% of participants had intrahepatic disease, the eligibility criteria based on FGFR2 status are relevant for the broader population.
Care Pathway Integration
Pemigatinib can be integrated into existing care pathways with minor adjustments. The committee noted that the treatment would require some planning and investment, particularly regarding genetic testing and monitoring, but overall, it fits well within current clinical practices.
Resource Use and Cost Implications
The resource implications of pemigatinib are manageable, with the potential for cost savings when considering the treatment’s effectiveness and the absence of other disease-modifying therapies. The committee concluded that the budget impact is justifiable given the expected benefits.
Evidence Quality and Robustness
The evidence base is primarily derived from a single-arm study, which introduces limitations in robustness. While the committee acknowledged the challenges of conducting trials in this rare cancer population, the reliance on indirect comparisons raises concerns about the overall quality of the evidence.
Uncertainty, Sensitivity, and Broader Impacts
The committee recognized the uncertainties surrounding the clinical evidence and cost-effectiveness estimates but noted that the treatment addresses a significant unmet need in a rare cancer population. The context of the treatment’s potential benefits helps mitigate some of the uncertainties.
