Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The evidence from the CheckMate 9ER trial indicates that cabozantinib plus nivolumab significantly improves overall survival (49.5 months vs. 35.5 months for sunitinib) and progression-free survival (16.6 months vs. 8.4 months for sunitinib). However, the evidence is uncertain regarding the effectiveness in different risk subgroups, which prevents a higher rating.
Cost effectiveness
The cost-effectiveness estimates for cabozantinib plus nivolumab are within the range that NICE considers acceptable for intermediate- and poor-risk cancer, although they are above acceptable levels for favourable-risk cancer. This suggests marginal cost-effectiveness overall.
Quality of life
Patient experts reported significant impacts on quality of life due to advanced renal cell carcinoma, indicating that treatment options like cabozantinib plus nivolumab could improve HRQoL. However, specific HRQoL data from validated instruments were not detailed in the document.
Supporting Domains
Safety and Adverse Effects
The treatment is reported to have a good safety profile, with manageable adverse effects compared to existing therapies. The document does not indicate any severe safety concerns that would undermine its value.
Comparator Selection
The treatment was compared against appropriate standard-of-care options, including sunitinib and combination therapies like nivolumab plus ipilimumab. The committee concluded that these were the most relevant comparators for the target population.
Patient Population and Subgroups
The trial population included a broad range of patients with advanced renal cell carcinoma, and the document discusses the relevance of different risk subgroups, although some limitations in subgroup analysis were noted.
Care Pathway Integration
The treatment can be integrated into existing care pathways with minor adjustments, as it aligns with current treatment protocols for advanced renal cell carcinoma.
Resource Use and Cost Implications
The economic model suggests that the resource implications are manageable, with cost-effectiveness estimates deemed acceptable for certain patient groups, indicating a reasonable budget impact.
Evidence Quality and Robustness
The evidence is primarily based on a well-conducted Phase III RCT (CheckMate 9ER) with a substantial sample size and follow-up duration, although some uncertainties in subgroup analyses were acknowledged.
Uncertainty, Sensitivity, and Broader Impacts
While there are uncertainties regarding the cost-effectiveness estimates, particularly for favourable-risk patients, the overall context supports the treatment’s use in the specified populations.
