Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The evidence indicates that nivolumab plus ipilimumab significantly improves progression-free survival compared to chemotherapy, with a 12-month progression-free survival rate of 78.7% versus 20.6% for chemotherapy. This demonstrates a clear clinical advantage, although the overall survival data is still maturing and carries some uncertainty.
Cost effectiveness
The cost-effectiveness estimates for nivolumab plus ipilimumab are within NICE’s acceptable range, with an ICER below £25,000 per QALY gained, indicating it is clearly cost-effective under common thresholds.
Quality of life
While specific HRQoL data is not extensively detailed, the committee noted that immunotherapies like nivolumab plus ipilimumab are generally better tolerated than chemotherapy, which suggests a moderate improvement in quality of life for patients.
Supporting Domains
Safety and Adverse Effects
The treatment has a very good safety profile, with mostly mild or moderate adverse events reported. The committee noted that immunotherapies are generally better tolerated than chemotherapy, which supports this rating.
Comparator Selection
Nivolumab plus ipilimumab was compared against appropriate standard-of-care treatments, including chemotherapy and pembrolizumab, which are relevant comparators for the target population.
Patient Population and Subgroups
The trial population is representative of the intended patient population with dMMR or MSI-H unresectable or metastatic colorectal cancer, although there are some limitations in subgroup analyses.
Care Pathway Integration
The treatment can be integrated into existing care pathways with minor adjustments, as it aligns with current clinical practices for treating colorectal cancer.
Resource Use and Cost Implications
The resource use estimates are manageable and align with Healthcare planning, indicating a notable but justifiable cost burden with proportional benefits.
Evidence Quality and Robustness
The evidence is based on robust clinical trials, including a phase 3 RCT, although there are some uncertainties regarding the overall survival data due to its immaturity.
Uncertainty, Sensitivity, and Broader Impacts
While there are uncertainties regarding long-term outcomes and the treatment effect compared to pembrolizumab, the context of unmet need and potential for improved outcomes supports a moderate rating.
