Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical evidence from the KEYNOTE-590 trial demonstrates that pembrolizumab, when added to platinum- and fluoropyrimidine-based chemotherapy, significantly improves both progression-free survival (7.5 months vs. 5.5 months) and overall survival (13.5 months vs. 9.4 months) for patients with locally advanced unresectable or metastatic oesophageal cancer whose tumours express PD-L1 with a CPS of 10 or more. This clear clinical advantage supports a rating of A+.
Cost effectiveness
The cost-effectiveness estimates for pembrolizumab with chemotherapy are likely to be within acceptable thresholds for Healthcare resources, as both the company’s and ERG’s models suggest ICERs below £50,000 per QALY. This indicates a strong economic value, supporting a rating of A+.
Quality of life
While the document indicates that advanced oesophageal cancer significantly impacts quality of life, it does not provide specific data on HRQoL improvements associated with pembrolizumab. However, the potential for improved survival and quality of life due to reduced symptoms suggests a moderate benefit, justifying an A rating.
Supporting Domains
Safety and Adverse Effects
The safety profile of pembrolizumab appears favorable, with the document indicating that adverse events are manageable and comparable to existing therapies. The committee noted that the addition of pembrolizumab does not significantly increase the treatment burden, supporting a rating of A+.
Comparator Selection
The document indicates that pembrolizumab is compared against dual chemotherapy regimens, which are the standard of care for this patient population. This appropriate comparator selection supports a rating of A.
Patient Population and Subgroups
The trial population is representative of the intended patient population, specifically focusing on those with PD-L1 expression of CPS 10 or more. The document discusses the generalizability of the trial results to Healthcare practice, supporting a rating of A+.
Care Pathway Integration
The integration of pembrolizumab into existing treatment pathways is described as manageable, with no significant new infrastructure or training required. This ease of integration supports a rating of A+.
Resource Use and Cost Implications
The document indicates that the budget impact of pembrolizumab is manageable and aligns with Healthcare planning. While there are concerns about resource burden, the overall implications are justifiable, supporting a rating of A.
Evidence Quality and Robustness
The evidence from the KEYNOTE-590 trial is robust, being a well-designed RCT with a significant sample size (n=749). However, some uncertainties regarding generalizability remain, justifying an A rating.
Uncertainty, Sensitivity, and Broader Impacts
While there are some uncertainties regarding the generalizability of the trial results and the extrapolation of overall survival, the context of unmet need and the potential benefits of the treatment mitigate these concerns, supporting an A rating.
