Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical evidence for tepotinib is based on the VISION trial, a single-arm study that suggests a clinical benefit but lacks comparative data against standard treatments. The objective response rate was reported at 46.7%, but the overall survival benefit was not statistically significant compared to chemotherapy or immunotherapy. The committee expressed concerns about the generalizability of the results to Healthcare practice, indicating substantial uncertainty in the clinical effectiveness of tepotinib.
Cost effectiveness
The cost-effectiveness estimates for tepotinib were reported to be within the range that NICE considers acceptable for Healthcare resources, particularly for the previously treated subgroup where end-of-life criteria were met. The ICERs were calculated with confidential discounts included, indicating a strong economic value proposition.
Quality of life
The committee noted that tepotinib offers a favorable side effect profile compared to chemotherapy and chemo-immunotherapy, which could lead to improvements in HRQoL. However, specific HRQoL data from validated instruments were not detailed in the document, leading to a moderate rating.
Supporting Domains
Safety and Adverse Effects
Tepotinib is described as well tolerated compared to standard chemotherapy options, with clinical experts indicating a favorable side effect profile. The document does not report significant adverse events that would undermine its use, supporting a very good safety rating.
Comparator Selection
The company did not initially compare tepotinib with specific comparators outlined in the NICE scope, instead using grouped treatment classes. However, subsequent analyses included relevant comparators like pembrolizumab plus pemetrexed and platinum, which aligns better with UK clinical practice. This indicates some limitations in the initial comparator selection.
Patient Population and Subgroups
The committee acknowledged that the majority of evidence is for untreated non-squamous NSCLC with METex14 skipping alterations, which is the key treatment population. The company provided analyses for previously treated and untreated populations, indicating a moderate level of representativeness.
Care Pathway Integration
Tepotinib is an oral treatment that does not require day-unit attendance, which facilitates its integration into existing care pathways. The committee noted that it would likely be offered as a first-line treatment, indicating manageable adjustments to current practices.
Resource Use and Cost Implications
The document indicates that tepotinib’s cost-effectiveness is acceptable, and the economic model captures its benefits. However, there are concerns about the overall resource burden, particularly regarding subsequent treatment assumptions, leading to a moderate rating.
Evidence Quality and Robustness
The evidence is primarily based on a single-arm trial, which introduces uncertainty. While the indirect treatment comparisons were made, the committee noted that the results were inconsistent and not robust, indicating a need for more rigorous evidence.
Uncertainty, Sensitivity, and Broader Impacts
There are significant uncertainties regarding the indirect treatment comparisons and overall survival extrapolations. The committee expressed concerns about the generalizability of the results to the UK population, indicating a high level of uncertainty.
