Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The evidence from the CheckMate 142 trial indicates that nivolumab plus ipilimumab significantly extends progression-free survival and overall survival in patients with metastatic colorectal cancer with high microsatellite instability or mismatch repair deficiency. Although the trial was single-arm and did not directly compare with standard treatments, indirect comparisons suggest substantial improvements in survival outcomes, justifying a rating of A+.
Cost effectiveness
The cost-effectiveness estimates for nivolumab plus ipilimumab are below £20,000 per QALY gained, which is within NICE’s acceptable threshold. This suggests a strong economic value for the treatment, meriting a rating of A+.
Quality of life
Patient experts reported that nivolumab with ipilimumab may lead to fewer debilitating side effects compared to traditional chemotherapy, thus potentially improving quality of life. However, the evidence is primarily anecdotal and lacks robust quantitative data, leading to a moderate rating of A.
Supporting Domains
Safety and Adverse Effects
The safety profile of nivolumab with ipilimumab is considered acceptable, with manageable adverse events reported. The treatment is noted to have a different safety profile compared to traditional chemotherapy, which is generally viewed positively, thus justifying a rating of A.
Comparator Selection
The treatment was not directly compared to standard care in the CheckMate 142 trial, which limits the strength of the evidence. The committee acknowledged that indirect comparisons were made, but the absence of head-to-head data leads to a B++ rating.
Patient Population and Subgroups
The population in CheckMate 142 is considered broadly generalizable to the Healthcare clinical practice, with a diverse group of patients who had previously undergone multiple treatments. This broad representation supports a rating of A+.
Care Pathway Integration
Nivolumab with ipilimumab can be integrated into existing treatment pathways with minor adjustments, as molecular testing for high MSI or MMR deficiency is already funded. This ease of integration supports a rating of A.
Resource Use and Cost Implications
The treatment is expected to have a manageable budget impact, with the potential for cost savings due to its effectiveness compared to traditional therapies. This positive outlook on resource use supports a rating of A+.
Evidence Quality and Robustness
The evidence from the CheckMate 142 trial is considered robust, although it is based on a single-arm study. The committee found the trial design acceptable for decision-making, leading to a rating of A.
Uncertainty, Sensitivity, and Broader Impacts
There are notable uncertainties regarding the indirect comparisons and the long-term survival extrapolations. These uncertainties, while acknowledged, do not negate the treatment’s potential benefits, resulting in a B++ rating.
