Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Sotorasib has been shown to increase the time before cancer progression and overall survival compared to docetaxel and docetaxel plus nintedanib in an indirect treatment comparison. However, the evidence is primarily based on a Phase 2 single-arm trial (CodeBreaK100), which does not provide the robust Phase 3 evidence required for a higher rating. The committee acknowledged the promising nature of the evidence but highlighted the uncertainty due to the lack of direct comparative data.
Cost effectiveness
The cost-effectiveness estimates for sotorasib are highly uncertain, primarily due to the reliance on an uncontrolled single-arm trial for clinical evidence and the use of unanchored indirect treatment comparisons. While there is potential for sotorasib to be cost-effective, the committee concluded that the current estimates exceed NICE’s acceptable thresholds, necessitating further evidence.
Quality of life
The evidence suggests that sotorasib, being an oral treatment, may improve health-related quality of life compared to intravenous chemotherapy, which is associated with more adverse effects and treatment burden. The committee noted that the utility estimates were plausible, although there are uncertainties in the data collection methods.
Supporting Domains
Safety and Adverse Effects
Sotorasib has a favorable safety profile with manageable adverse effects, particularly when compared to traditional chemotherapy options. The committee noted that the adverse events reported were mostly mild to moderate, supporting a good tolerability rating.
Comparator Selection
The clinical evidence for sotorasib was primarily compared to docetaxel and docetaxel plus nintedanib, which are relevant comparators. However, the absence of direct head-to-head trials introduces uncertainty, and the committee noted that the company did not provide evidence comparing sotorasib with platinum-doublet chemotherapy, which is a significant treatment option.
Patient Population and Subgroups
The trial population in the CodeBreaK100 study included a diverse group of patients with KRAS G12C mutation-positive NSCLC, which is representative of the intended patient population. However, there are some limitations in subgroup analyses that could affect generalizability.
Care Pathway Integration
Sotorasib is an oral treatment that can be integrated into existing care pathways with minimal disruption. The committee noted that it is less resource-intensive compared to intravenous therapies, which aligns well with current clinical practices.
Resource Use and Cost Implications
While sotorasib is expected to be less resource-intensive than traditional chemotherapy, the overall budget impact remains uncertain due to the high cost of the treatment and the need for further evidence to support its cost-effectiveness. The committee expressed concerns about the potential high resource burden.
Evidence Quality and Robustness
The evidence base for sotorasib is primarily derived from a Phase 2 trial, which raises concerns about robustness and generalizability. The committee acknowledged the promising results but emphasized the need for more rigorous Phase 3 data to strengthen the evidence base.
Uncertainty, Sensitivity, and Broader Impacts
There are significant uncertainties surrounding the clinical effectiveness and cost-effectiveness of sotorasib, particularly due to the reliance on indirect comparisons and the lack of direct trial evidence. The committee noted that these uncertainties could impact decision-making and access to the treatment.
