Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Entrectinib shows a moderate benefit over current care, with a high overall response rate of 73.4% and a median progression-free survival of 16.8 months in the STARTRK-2 trial. However, the evidence is based on a single-arm trial and indirect comparisons, which introduces uncertainty regarding its effectiveness compared to standard treatments. This strengthens the market access risk assessment and overall reimbursement probability.
Cost effectiveness
The cost-effectiveness estimates for entrectinib are within the range NICE considers acceptable for end-of-life treatments, with an ICER ranging from £21,607 to £42,572 per QALY gained. This suggests a clear cost-effective profile under common thresholds. This informs pricing and reimbursement risk and pharmaceutical reimbursement forecasting.
Quality of life
The document does not provide specific data on HRQoL improvements associated with entrectinib. While the treatment is expected to delay chemotherapy and is valued by patients, there is no substantial evidence of significant improvements in quality of life metrics. These outcomes align with HTA decision predictors and support pricing and reimbursement assessment.
Supporting Domains
Safety and Adverse Effects
Entrectinib is reported to have a good safety profile, with manageable adverse events. The document indicates that the adverse effects are mostly mild to moderate, aligning with the safety profiles of existing therapies. This profile reduces payer uncertainty and supports access risk forecasting.
Comparator Selection
The main comparator, pemetrexed with platinum chemotherapy, is appropriate; however, the evidence for this comparator is derived from ALK-positive NSCLC studies, which introduces uncertainty regarding the validity of the comparisons made. This aligns with HTA comparator analysis and strengthens the market access submission.
Patient Population and Subgroups
The trial population is considered representative of the intended patient population, specifically focusing on adults with ROS1-positive advanced NSCLC. The document discusses the inclusion of relevant subgroups, although the overall sample size is small. This enhances reimbursement likelihood rating and payer relevance.
Care Pathway Integration
Entrectinib can be integrated into existing treatment pathways with minor adjustments, as it is an oral treatment that can delay the need for chemotherapy, which is favorable for both patients and clinicians. This supports budget impact analysis and facilitates market access feasibility.
Resource Use and Cost Implications
The resource implications of using entrectinib are manageable, with the potential for cost savings due to its oral administration and the ability to delay chemotherapy. The commercial arrangement also supports its affordability. This supports pricing model stress-testing and payer evidence expectations.
Evidence Quality and Robustness
The evidence base includes data from a single-arm trial and indirect comparisons, which raises concerns about robustness and potential biases. While the results are promising, the reliance on proxy data introduces uncertainty. These outcomes align with HTA decision predictors and support pricing and reimbursement assessment.
Uncertainty, Sensitivity, and Broader Impacts
There are significant uncertainties regarding the survival estimates and the effectiveness of entrectinib compared to standard treatments, particularly due to the use of indirect comparisons and the small patient population. These factors elevate access risk forecasting within HTA evaluation frameworks.
