Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The CAPItello-291 trial demonstrated that capivasertib plus fulvestrant significantly improved progression-free survival compared to placebo plus fulvestrant (median 7.3 months vs. 3.1 months). Although overall survival data was not statistically significant, the improvement in progression-free survival indicates a clear clinical advantage over existing treatments.
Cost effectiveness
The ICER for capivasertib plus fulvestrant is below £20,000 per QALY gained when considering the committee’s preferred assumptions. This indicates that the treatment is clearly cost-effective under common thresholds, especially given the high unmet need in this patient population.
Quality of life
The treatment is expected to have a better tolerability profile compared to alpelisib plus fulvestrant, which is associated with significant toxicity. The EQ-5D-5L was used to measure quality of life, and while the utility values are confidential, the committee acknowledged that capivasertib plus fulvestrant likely leads to better quality of life outcomes.
Supporting Domains
Safety and Adverse Effects
Capivasertib plus fulvestrant has a very good safety profile, with manageable adverse events compared to existing therapies. The committee noted that the treatment’s toxicity is much lower than that of alpelisib plus fulvestrant, which is associated with significant side effects.
Comparator Selection
The treatment was not directly compared with alpelisib plus fulvestrant in clinical trials, which is a limitation. However, indirect comparisons suggest comparable efficacy. The committee concluded that the relevant comparators were appropriately selected.
Patient Population and Subgroups
The patient population for capivasertib plus fulvestrant is well-defined, focusing on those with specific gene alterations after prior treatment. The committee recognized the high unmet need in this subgroup, which enhances the treatment’s relevance.
Care Pathway Integration
Capivasertib plus fulvestrant can be integrated into existing treatment pathways with minor adjustments. The treatment aligns with current clinical practices for managing advanced breast cancer, requiring no significant new infrastructure.
Resource Use and Cost Implications
The overall budget impact is manageable, especially considering the treatment’s cost-effectiveness. The inclusion of genomic testing costs was addressed, and the committee found the estimates reasonable.
Evidence Quality and Robustness
The evidence base is strong, primarily derived from the CAPItello-291 trial, which is a Phase 3 RCT. While there are some uncertainties regarding indirect comparisons, the overall evidence quality is acceptable.
Uncertainty, Sensitivity, and Broader Impacts
While there are uncertainties related to the indirect comparisons and treatment effects, the committee noted that the fractional polynomial analyses reduced uncertainty significantly. The treatment addresses a high unmet need, which is a favorable context.
