Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The evidence from the KEYNOTE-189 trial indicates that pembrolizumab combination therapy significantly improves overall survival compared to pemetrexed platinum chemotherapy, with a hazard ratio of 0.56. However, the lack of direct comparisons with pembrolizumab monotherapy for the high PD-L1 subgroup introduces some uncertainty.
Cost effectiveness
The cost-effectiveness estimates for pembrolizumab combination therapy are within the acceptable range for Healthcare resources, particularly when considering the 2-year stopping rule. The ICERs are below £50,000 per QALY gained, which is favorable.
Quality of life
The document indicates that no new data on health-related quality of life was presented, and the committee preferred to use previously established utility values. This suggests minimal impact on HRQoL was demonstrated, leading to a mixed assessment.
Supporting Domains
Safety and Adverse Effects
The safety profile of pembrolizumab combination therapy is acceptable, with manageable adverse events. The document does not highlight significant safety concerns compared to existing therapies.
Comparator Selection
The comparators selected for the appraisal, including pemetrexed platinum chemotherapy and pembrolizumab monotherapy, are appropriate and relevant to the patient population being studied.
Patient Population and Subgroups
The trial population is broadly representative of the intended patient population, although there are some limitations in subgroup analyses, particularly regarding the high PD-L1 subgroup.
Care Pathway Integration
The integration of pembrolizumab combination therapy into existing care pathways appears manageable, with only minor adjustments needed for implementation.
Resource Use and Cost Implications
The resource implications of pembrolizumab combination therapy are considered manageable, with the potential for cost savings due to its effectiveness compared to standard care.
Evidence Quality and Robustness
The evidence base is strong, primarily derived from a Phase 3 RCT (KEYNOTE-189), although some uncertainties remain regarding the long-term outcomes and indirect comparisons.
Uncertainty, Sensitivity, and Broader Impacts
There are notable uncertainties regarding the long-term effectiveness and cost-effectiveness of pembrolizumab combination therapy, particularly in the high PD-L1 subgroup, which may impact broader implementation.
