Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The evidence indicates that atezolizumab has comparable efficacy to pembrolizumab based on an indirect comparison, but there is no direct evidence from head-to-head trials. The IMpower110 trial showed that atezolizumab improves overall survival and progression-free survival compared to chemotherapy, but the lack of direct comparison with pembrolizumab introduces uncertainty. Therefore, it meets non-inferiority but does not demonstrate a clear edge.
Cost effectiveness
The cost-effectiveness analysis indicates that atezolizumab is cost-saving compared to pembrolizumab, with positive incremental net health benefits at NICE’s acceptable thresholds. The committee concluded that the likelihood of atezolizumab being cost-effective is high, supporting its use within Healthcare resources.
Quality of life
The document does not provide specific data on HRQoL improvements associated with atezolizumab compared to pembrolizumab. While the treatment is expected to improve quality of life due to its mechanism, the absence of validated tools or significant domain-specific improvements leads to a rating of no demonstrated benefit.
Supporting Domains
Safety and Adverse Effects
Atezolizumab is reported to have a good safety profile with no robust differences in toxicity compared to pembrolizumab. The absence of significant adverse events undermining the treatment’s benefits supports a rating of acceptable safety with some concerns.
Comparator Selection
The main comparator for atezolizumab is pembrolizumab monotherapy, which is appropriate given the treatment landscape for untreated high PD-L1-expression metastatic NSCLC. The committee recognized that pembrolizumab is the standard of care, and the selection aligns with current clinical practice.
Patient Population and Subgroups
The trial population for atezolizumab is representative of the intended patient population with untreated high PD-L1-expression metastatic NSCLC. The focus on TC3 and IC3 subpopulations aligns with the marketing authorization, although some subgroup gaps exist.
Care Pathway Integration
Atezolizumab can be integrated into existing care pathways with minor adjustments, as it does not require new infrastructure or significant changes in clinical practice. The committee noted that the approval of atezolizumab would not necessitate changes in the use of PD-L1 assays in clinical practice.
Resource Use and Cost Implications
The budget impact analysis indicates that atezolizumab has a manageable budget impact aligned with planning, as it is associated with cost savings compared to pembrolizumab. The committee concluded that the resource implications are justifiable given the treatment’s benefits.
Evidence Quality and Robustness
The evidence base is primarily derived from the IMpower110 trial, a Phase 3 RCT, which is robust but has some limitations due to the lack of direct comparisons with pembrolizumab. The committee acknowledged the potential biases in the indirect comparisons but considered the overall evidence acceptable.
Uncertainty, Sensitivity, and Broader Impacts
There are notable uncertainties regarding the duration of treatment effects and the comparability of PD-L1 assays used in different studies. While the committee recognized these uncertainties, they concluded that the overall context supports the use of atezolizumab, albeit with caution.
