Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The NATALEE trial demonstrated a statistically significant improvement in invasive disease-free survival (iDFS) for ribociclib plus an aromatase inhibitor compared to an aromatase inhibitor alone (HR 0.715, p<0.0001). However, the overall survival (OS) data remains uncertain as it is still ongoing, and the committee noted that the clinical-effectiveness results were highly uncertain due to the small number of events observed. Therefore, while there is moderate benefit, the uncertainty regarding long-term outcomes limits the rating to A.
Cost effectiveness
The cost-effectiveness estimates for ribociclib plus an aromatase inhibitor were found to be below the committee’s preferred threshold of £20,000 per QALY gained, indicating that it is a cost-effective use of NHS resources. The committee concluded that the treatment provides good value for money, thus justifying a rating of A+.
Quality of life
The model utilized utility values derived from EQ-5D-5L data collected in the NATALEE trial, indicating that ribociclib plus an aromatase inhibitor is expected to maintain a good quality of life. The committee acknowledged that the treatment is likely to improve HRQoL, particularly as it is an oral treatment, which may enhance adherence. However, the exact impact on HRQoL remains somewhat uncertain, justifying a rating of A.
Supporting Domains
Safety and Adverse Effects
Ribociclib has a favorable safety profile, with most adverse events being mild to moderate. The committee noted that while there are some concerns regarding adverse effects, they are manageable and do not significantly undermine the overall value of the treatment. This strong tolerability supports a rating of A+.
Comparator Selection
The comparators used in the NATALEE trial were appropriate, primarily comparing ribociclib plus an aromatase inhibitor against an aromatase inhibitor alone. The committee also acknowledged that while there was no direct comparison with abemaciclib, indirect comparisons were made, which were deemed acceptable. This supports a rating of A.
Patient Population and Subgroups
The trial population in NATALEE was well-defined and aligned with the marketing authorization, including relevant subgroups. The committee noted that the population was representative of those who would be treated in clinical practice, which supports a rating of A+.
Care Pathway Integration
Ribociclib can be integrated into existing care pathways with minimal disruption, as it is an oral treatment that does not require significant changes to current practices. The committee noted that while some adjustments may be necessary, they are manageable, justifying a rating of A.
Resource Use and Cost Implications
The budget impact of ribociclib is considered manageable, with the potential for cost savings due to its effectiveness in reducing recurrence. The committee concluded that the resource implications are justifiable, supporting a rating of A.
Evidence Quality and Robustness
The evidence base is supported by a robust Phase 3 trial (NATALEE) with a large sample size and low risk of bias. However, the ongoing nature of some outcomes introduces some uncertainty, which prevents a higher rating. Thus, a rating of A is appropriate.
Uncertainty, Sensitivity, and Broader Impacts
While there are uncertainties related to long-term outcomes and treatment effects, the committee found these uncertainties manageable within the context of the unmet need for effective treatments. This context supports a rating of A.
