Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The evidence from the CheckMate 743 trial indicates that nivolumab plus ipilimumab improves overall survival compared to chemotherapy, with a median overall survival of 18.1 months versus 14.1 months for chemotherapy. The hazard ratios at both the 2-year and 3-year follow-ups suggest a sustained treatment effect, although there is some uncertainty regarding long-term outcomes.
Cost effectiveness
The cost-effectiveness estimates for nivolumab plus ipilimumab are reported to be less than £50,000 per QALY gained, which is within the range considered acceptable by NICE. This suggests a favorable economic profile for the treatment.
Quality of life
The CheckMate 743 trial showed a trend towards improvement in quality of life as measured by the EQ-5D-3L utility index, with scores increasing from 0.70 at baseline to 0.84 at week 72 for the nivolumab plus ipilimumab arm. However, the lack of a statistically significant group difference at the 2-year data cut limits the strength of this evidence.
Supporting Domains
Safety and Adverse Effects
The safety profile of nivolumab plus ipilimumab is considered acceptable, with a higher incidence of severe treatment-related adverse events compared to chemotherapy, but manageable. The committee noted that most adverse events resolved, indicating a generally tolerable safety profile.
Comparator Selection
The treatment was compared against the appropriate standard of care, which is platinum-doublet chemotherapy. The committee concluded that chemotherapy is the only relevant comparator for nivolumab plus ipilimumab as a first-line treatment option.
Patient Population and Subgroups
The trial population included adults with ECOG performance status of 0 or 1, which is representative of the intended patient population in the UK. The committee noted that the trial population was generalizable to patients seen in Healthcare practice.
Care Pathway Integration
Nivolumab plus ipilimumab can be integrated into existing healthcare pathways with minor adjustments. The treatment does not require new infrastructure or extensive training, making it a feasible option for implementation.
Resource Use and Cost Implications
The budget impact of nivolumab plus ipilimumab is manageable, and the treatment is expected to provide significant benefits relative to its costs. The committee noted that the economic model supports its use within the Healthcare.
Evidence Quality and Robustness
The evidence base is supported by a phase 3 RCT (CheckMate 743) with a robust design, although there are some uncertainties regarding long-term outcomes and the extrapolation of survival data.
Uncertainty, Sensitivity, and Broader Impacts
While there are uncertainties regarding the long-term treatment effects and the extrapolation of survival data, the context of unmet need and the potential benefits of the treatment provide a favorable backdrop for its use.
