Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical evidence for dostarlimab primarily comes from the ongoing GARNET trial, which is a single-arm study. While it suggests that dostarlimab may improve progression-free survival and overall survival compared to current treatments, the lack of direct comparisons and the immaturity of the data lead to significant uncertainty. The committee noted that indirect comparisons with other treatments are highly uncertain due to differences in study populations.
Cost effectiveness
The economic model suggests that dostarlimab has the potential to be cost-effective, but the committee highlighted that the ICER is uncertain due to the immaturity of the trial data and the reliance on indirect comparisons. The ICER was reported at £38,363 per QALY, which is within acceptable limits, but the committee expressed concerns about the robustness of this estimate.
Quality of life
Patient experts indicated that dostarlimab is associated with fewer serious adverse events compared to chemotherapy, which is expected to improve quality of life. The treatment’s shorter administration time also reduces the treatment burden, contributing positively to HRQoL. However, the evidence is primarily anecdotal and lacks robust quantitative data.
Supporting Domains
Safety and Adverse Effects
Dostarlimab is reported to have a manageable adverse event profile, with lower rates of serious adverse events compared to standard chemotherapy. The clinical experts noted that adverse events were generally low grade, supporting a favorable safety profile.
Comparator Selection
The evidence for dostarlimab lacks direct comparisons with standard treatments, relying instead on indirect treatment comparisons that are fraught with uncertainty. The committee acknowledged that while KEYNOTE-775 provides relevant comparator data, the absence of a biomarker-matched comparator arm in GARNET limits the robustness of the evidence.
Patient Population and Subgroups
The GARNET trial population is somewhat representative of the intended patient population, but there are concerns regarding the generalizability of the results due to the lack of biomarker data in the RWE subgroup. The committee noted significant differences in patient characteristics between the GARNET and RWE populations.
Care Pathway Integration
Dostarlimab can be integrated into existing care pathways with minor adjustments, primarily due to its shorter administration time compared to traditional chemotherapy. This makes it a more convenient option for patients, which is a positive aspect for integration into clinical practice.
Resource Use and Cost Implications
While dostarlimab is expected to have a manageable budget impact, the committee raised concerns about the overall resource burden due to uncertainties in the economic model and the need for further data collection to confirm cost-effectiveness.
Evidence Quality and Robustness
The evidence base is primarily derived from a single-arm trial, which presents limitations in terms of robustness and potential biases. The committee noted that while the GARNET trial provides some insights, the lack of direct comparative data and the ongoing nature of the trial contribute to significant uncertainty.
Uncertainty, Sensitivity, and Broader Impacts
There is considerable uncertainty surrounding the long-term outcomes and cost-effectiveness of dostarlimab due to the immaturity of the trial data and the reliance on indirect comparisons. The committee emphasized the need for further data collection to address these uncertainties.
