Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical evidence from the KEYNOTE-826 trial demonstrates a clear clinical advantage for pembrolizumab plus chemotherapy with or without bevacizumab, showing significant improvements in both progression-free survival (PFS) and overall survival (OS) compared to standard care. The median PFS was 10.5 months versus 8.2 months for the placebo group, and median OS was 28.6 months versus 16.5 months, indicating a substantial therapeutic benefit.
Cost effectiveness
The cost-effectiveness estimates for pembrolizumab plus chemotherapy are within the acceptable range for Healthcare resources, particularly when considering the end-of-life criteria. The committee concluded that the ICERs were substantially below the acceptable level of £50,000 per QALY gained, indicating a strong economic value.
Quality of life
While the document does not provide extensive HRQoL data, it indicates that the treatment aims to improve quality of life by managing symptoms and extending life. The committee noted the substantial disruption to quality of life caused by the disease, suggesting that any treatment prolonging life while managing symptoms would positively impact HRQoL.
Supporting Domains
Safety and Adverse Effects
The safety profile of pembrolizumab plus chemotherapy is acceptable, with manageable adverse events reported. The committee did not highlight any significant safety concerns that would undermine the treatment’s benefits, suggesting a good tolerability profile.
Comparator Selection
The treatment was compared against standard care, which includes chemotherapy with or without bevacizumab. This is appropriate as it reflects the current treatment landscape for persistent, recurrent, or metastatic cervical cancer, ensuring relevant and meaningful comparisons.
Patient Population and Subgroups
The trial population in KEYNOTE-826 is representative of the intended patient population, focusing on adults with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1. The committee noted that the trial results were generalizable to the Healthcare population, supporting the relevance of the findings.
Care Pathway Integration
Pembrolizumab can be integrated into existing treatment pathways with manageable adjustments. The committee indicated that the treatment aligns with current clinical practices, requiring no significant new infrastructure or training.
Resource Use and Cost Implications
The budget impact of pembrolizumab is manageable, with the potential for cost savings due to its effectiveness in extending life and improving quality of life. The committee’s conclusion that the ICERs are below acceptable thresholds supports this rating.
Evidence Quality and Robustness
The evidence is robust, based on a Phase 3 RCT (KEYNOTE-826) with a significant patient population and mature data. The committee noted that the final analysis strengthened the clinical evidence, providing a high level of confidence in the findings.
Uncertainty, Sensitivity, and Broader Impacts
While there is some uncertainty regarding long-term benefits, particularly for patients whose cancer responds well to treatment, the committee concluded that the overall context supports the use of pembrolizumab. The treatment addresses a significant unmet need in a high-burden disease area.
