Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The evidence from the KEYNOTE-775 trial indicates that pembrolizumab plus lenvatinib significantly improves both progression-free survival (7.3 months vs. 3.8 months) and overall survival (18.7 months vs. 11.9 months) compared to doxorubicin or paclitaxel monotherapy. The hazard ratios (HR) of 0.56 and 0.65 demonstrate a clear clinical advantage, although the results are somewhat uncertain due to the use of non-standard treatments in the trial following non-platinum-based chemotherapy.
Cost effectiveness
The cost-effectiveness estimates for pembrolizumab plus lenvatinib are reported to be less than £50,000 per QALY gained, which is within acceptable thresholds for end-of-life treatments. The economic model, while having some uncertainties, supports the treatment’s cost-effectiveness under the current commercial arrangements.
Quality of life
Patient experts reported significant improvements in quality of life after receiving pembrolizumab plus lenvatinib, allowing them to engage in sports and social activities. The treatment is perceived as less burdensome compared to traditional chemotherapy, which aligns with moderate improvements in HRQoL, although specific validated tools were not extensively detailed.
Supporting Domains
Safety and Adverse Effects
The safety profile of pembrolizumab plus lenvatinib is considered acceptable, with mostly mild to moderate adverse events reported. The committee noted that the treatment is well tolerated compared to traditional chemotherapy, which often has more severe side effects.
Comparator Selection
The treatment was compared against doxorubicin or paclitaxel monotherapy, which are appropriate comparators for patients who have progressed after platinum-based chemotherapy. However, the committee acknowledged that there is no standard second-line treatment, which raises some concerns about the robustness of the comparator selection.
Patient Population and Subgroups
The trial population in KEYNOTE-775 is considered generalizable to the Healthcare, with a representative sample of patients who have advanced or recurrent endometrial cancer. The committee noted that while there are some differences in age and weight, these do not significantly impact the treatment’s applicability to the broader patient population.
Care Pathway Integration
Pembrolizumab plus lenvatinib can be integrated into existing care pathways with minor adjustments. The treatment does not require new infrastructure or extensive training, making it a feasible option for healthcare providers.
Resource Use and Cost Implications
The treatment is expected to have a manageable budget impact, with the potential for cost savings due to its effectiveness in extending life compared to current options. The economic model suggests that the resource use is justifiable given the benefits provided.
Evidence Quality and Robustness
The evidence base is supported by a well-conducted Phase III trial (KEYNOTE-775) with a robust design. While there are some uncertainties regarding the generalizability of the results, the overall quality of evidence is strong.
Uncertainty, Sensitivity, and Broader Impacts
There are notable uncertainties regarding the long-term effects of treatment and the economic model assumptions, particularly concerning treatment waning and the impact of subsequent therapies. These uncertainties may affect the overall decision-making process.
