Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical trial evidence from the RELATIVITY-047 trial indicates that nivolumab-relatlimab provides a clear clinical advantage over nivolumab monotherapy, with longer progression-free survival (PFS) of 10.2 months compared to 4.6 months for nivolumab. Although there is no direct evidence comparing it with pembrolizumab or nivolumab plus ipilimumab, indirect comparisons suggest similar or superior outcomes. However, the uncertainty in overall survival data prevents a higher rating.
Cost effectiveness
The cost-effectiveness estimates for nivolumab-relatlimab are at or below the lower end of NICE’s acceptable range, indicating marginal cost-effectiveness. The committee concluded that the ICERs were acceptable given the uncertainty in overall survival, supporting a defensible position for cost-effectiveness.
Quality of life
The document does not provide specific data on HRQoL improvements associated with nivolumab-relatlimab. While it is suggested that the treatment is better tolerated than nivolumab plus ipilimumab, the lack of validated tools or substantial evidence on quality-of-life gains leads to a B++ rating.
Supporting Domains
Safety and Adverse Effects
Nivolumab-relatlimab has a very good safety profile, with adverse events primarily being mild to moderate. The committee noted that it is better tolerated than nivolumab plus ipilimumab, which supports a strong rating for safety.
Comparator Selection
While nivolumab-relatlimab was compared with nivolumab in the RELATIVITY-047 trial, there is no direct evidence against pembrolizumab or nivolumab plus ipilimumab. The reliance on indirect comparisons raises concerns about the robustness of the evidence, leading to a B++ rating.
Patient Population and Subgroups
The trial population in RELATIVITY-047 is considered to be representative of the intended patient population, including adolescents aged 12 years and older. The committee concluded that the trial data could be generalized to the broader population, supporting a moderate rating.
Care Pathway Integration
Nivolumab-relatlimab can be integrated into existing treatment pathways with minor adjustments, as it is positioned as an alternative when nivolumab plus ipilimumab is unsuitable. This indicates a good fit within current clinical practice.
Resource Use and Cost Implications
The economic model indicates that nivolumab-relatlimab has a manageable budget impact, especially with the commercial arrangement providing a discount. This suggests a good resource use profile, justifying a rating of A.
Evidence Quality and Robustness
The evidence from the RELATIVITY-047 trial is robust, being a phase 2/3 RCT with a reasonable sample size. However, the reliance on indirect comparisons and some methodological concerns prevent a higher rating.
Uncertainty, Sensitivity, and Broader Impacts
There is considerable uncertainty surrounding long-term overall survival estimates, which affects the cost-effectiveness conclusions. The committee noted that this uncertainty could restrict the use of nivolumab-relatlimab, leading to a B++ rating.
