Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The evidence from the ADAURA trial demonstrates that osimertinib significantly improves disease-free survival (DFS) and overall survival (OS) compared to placebo, with a median DFS of 65.8 months versus 28.1 months for placebo. The hazard ratios indicate a substantial reduction in the risk of recurrence and mortality, supporting a clear clinical advantage. However, long-term effectiveness remains uncertain due to the low number of events in the osimertinib arm.
Cost effectiveness
The cost-effectiveness estimates for osimertinib are within the range that NICE considers acceptable, with an ICER around £20,000 per QALY gained. This suggests that the treatment provides a defensible economic value relative to its benefits, although uncertainties remain regarding long-term outcomes and retreatment rates.
Quality of life
While specific HRQoL data is not extensively detailed, the committee noted that osimertinib is associated with lower anxiety regarding cancer recurrence and is generally well-tolerated, which suggests a moderate improvement in quality of life for patients. The treatment’s tolerability and the reduction in the fear of recurrence contribute positively to patient well-being.
Supporting Domains
Safety and Adverse Effects
Osimertinib has a very good safety profile, with limited side effects that are manageable and unlikely to lead to treatment discontinuation. The committee noted that the adverse events reported were mostly mild to moderate, indicating a favorable tolerability compared to existing treatments.
Comparator Selection
The comparator used in the clinical trials was appropriate, with osimertinib being compared to placebo in the ADAURA trial. The committee concluded that active monitoring is the relevant comparator in this context, as there are no other adjuvant treatment options available for this patient population.
Patient Population and Subgroups
The trial population is broadly representative of the intended patient population, with subgroup analyses conducted for stages 1b and 2-3a. While there are some concerns regarding the smaller subgroup data, the overall population covered is adequate for decision-making.
Care Pathway Integration
Osimertinib can be integrated into existing care pathways with minor adjustments, as it is intended to be used alongside or following standard chemotherapy. The treatment does not require significant changes to current clinical practices, making it a seamless fit for healthcare providers.
Resource Use and Cost Implications
The budget impact of osimertinib is manageable, with the treatment being cost-effective under NICE’s thresholds. The committee noted that the economic model accounted for relevant costs, including EGFR testing, which supports the treatment’s viability within the Healthcare budget.
Evidence Quality and Robustness
The evidence base is strong, primarily derived from the Phase 3 ADAURA trial, which is well-designed and provides robust data. However, there are some limitations regarding long-term follow-up and the maturity of the data, which introduces some uncertainty.
Uncertainty, Sensitivity, and Broader Impacts
While there are uncertainties regarding long-term outcomes and the economic model, the committee noted that these are manageable within the context of unmet need and the potential benefits of osimertinib. The treatment addresses a significant gap in care for patients with EGFR mutation-positive NSCLC.
