Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The evidence from the SERENA-2 trial indicates that camizestrant shows comparable efficacy to fulvestrant, with median progression-free survival (PFS) of 7.2 months for 75 mg and 7.7 months for 150 mg versus 3.7 months for fulvestrant. However, the trial is phase II and open-label, which limits confidence in the findings. The SERENA-6 trial, while showing stronger efficacy in an earlier-switch setting, does not directly address the post-progression population requested, leading to a lack of clarity on the treatment’s effectiveness in that specific context.
Cost effectiveness
There is no public economic evidence available for camizestrant, including ICER or cost-utility models. The absence of economic data makes it impossible to evaluate its cost-effectiveness, leading to a classification of non-cost-effective due to lack of evidence.
Quality of life
While SERENA-6 reported improvements in quality of life metrics, including delayed deterioration in global health status, there is no utility data available for QALY modeling. The absence of EQ-5D or similar utility measures limits the ability to assess the overall impact on HRQoL, leading to a conclusion of no demonstrated benefit in this area.
Supporting Domains
Safety and Adverse Effects
Camizestrant has a moderate safety profile, with treatment-related adverse events occurring in 53% to 70% of patients across different doses. Serious adverse events were relatively low, and no treatment-related deaths were reported. However, there are concerns regarding dose-dependent bradycardia and QTc prolongation, which require monitoring.
Comparator Selection
The SERENA-2 trial used fulvestrant as a comparator, which is relevant for the post-progression setting. However, the SERENA-6 trial’s comparator of continued aromatase inhibitor plus CDK4/6 inhibitor is less relevant for the requested indication, leading to concerns about the appropriateness of the comparators used.
Patient Population and Subgroups
The patient population in SERENA-2 is limited to postmenopausal women, which narrows generalizability to other demographics. While SERENA-6 includes a broader population, it focuses on an earlier molecularly selected subgroup, which does not fully represent the requested post-progression population.
Care Pathway Integration
The integration of camizestrant into existing care pathways is expected to require significant adjustments, including new diagnostic workflows and monitoring protocols. This complexity indicates a substantial impact on current practices, leading to a moderate rating.
Resource Use and Cost Implications
There is no available economic model or budget impact analysis for camizestrant, making it impossible to assess its resource implications. The lack of data on direct medical costs and implementation costs leads to a classification of unsustainable budget impact.
Evidence Quality and Robustness
The evidence base includes randomized trials, but the phase II nature of SERENA-2 and the mismatch of SERENA-6 with the requested indication create gaps in the robustness of the evidence. The overall quality is moderate due to these limitations.
Uncertainty, Sensitivity, and Broader Impacts
There are significant uncertainties regarding the long-term benefits of camizestrant, particularly in the context of the requested post-progression indication. The regulatory split and differing interpretations of the evidence add to the uncertainty, leading to a moderate rating.
