Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Pembrolizumab shows moderate benefit over current care, with evidence from the KEYNOTE-177 trial indicating a 40% increase in progression-free survival compared to standard care. However, the overall survival data is immature and uncertain due to crossover and the trial’s exclusion of certain standard treatments available in the Healthcare.
Cost effectiveness
The cost-effectiveness estimates for pembrolizumab are within NICE’s acceptable thresholds, with ICERs below £20,000 per QALY gained against all comparators. The economic model is deemed appropriate for decision-making.
Quality of life
Patient experts reported significant improvements in quality of life with pembrolizumab compared to standard chemotherapy, citing fewer side effects and a more manageable treatment regimen. The evidence suggests strong domain-specific improvements, although some disutility for adverse events was included in the model.
Supporting Domains
Safety and Adverse Effects
Pembrolizumab has an acceptable safety profile, with a lower incidence of serious adverse events compared to standard care. Although some rare serious adverse events were not included in the economic model, the overall tolerability is considered good.
Comparator Selection
The KEYNOTE-177 trial used a blended comparator approach that does not fully reflect Healthcare practice, as it included treatments not recommended in the Healthcare. This raises concerns about the validity of the comparisons made.
Patient Population and Subgroups
The trial population is representative of the intended patient population with high MSI or MMR deficiency. However, there are concerns regarding the small subgroup analyses for RAS-mutant patients, which may limit generalizability.
Care Pathway Integration
Pembrolizumab can be integrated into existing care pathways with minor adjustments, as it requires no new infrastructure and aligns with current treatment practices for eligible patients.
Resource Use and Cost Implications
The resource implications of pembrolizumab are manageable, with the potential for cost savings due to reduced hospitalizations and treatment burden compared to standard chemotherapy.
Evidence Quality and Robustness
The evidence base is strong, primarily derived from a Phase 3 RCT (KEYNOTE-177), although there are some methodological concerns regarding the comparators and the generalizability of results.
Uncertainty, Sensitivity, and Broader Impacts
There are notable uncertainties regarding the long-term benefits of pembrolizumab, particularly due to the crossover in the trial and the lack of data on its effectiveness beyond 2 years. This uncertainty may impact broader adoption.
