Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The evidence from the DeLLphi-301 trial indicates a 40% objective response rate (ORR) and a median duration of response of 9.7 months, which is clinically meaningful in a population where standard treatments have historically shown lower response rates. However, the lack of a randomized comparator in this specific later-line population limits the confidence in comparative efficacy, leading to a B++ rating.
Cost effectiveness
The cost-effectiveness analyses from NICE and CDA-AMC indicate that the ICERs are above acceptable thresholds, with NICE’s preferred ICER at £35,393 per QALY being deemed too uncertain. This suggests questionable cost-effectiveness, leading to a B+ rating.
Quality of life
The HRQoL data from the DeLLphi-301 trial show improvements in global health status and stabilization of symptoms like dyspnea, with validated instruments used for assessment. Although the evidence is not fully comprehensive for economic use, the positive trends and the use of validated tools support a rating of A.
Supporting Domains
Safety and Adverse Effects
The safety profile of tarlatamab shows a high incidence of cytokine release syndrome (CRS), but it is generally manageable, with serious adverse events being relatively low. The overall safety and tolerability are characterized as acceptable, supporting a rating of A+.
Comparator Selection
The DeLLphi-301 trial did not include a comparator, relying instead on external controls for indirect comparisons. This lack of direct comparative evidence in the exact later-line population leads to a B rating due to significant concerns regarding the validity of the comparisons.
Patient Population and Subgroups
The trial population primarily consisted of patients with ECOG 0-1, which may not fully represent the broader real-world population of patients with relapsed ES-SCLC. While there is some subgroup data from Asia, the overall representativeness is limited, justifying a B++ rating.
Care Pathway Integration
Tarlatamab requires specific monitoring and training for healthcare providers, indicating significant integration challenges into existing care pathways. The need for additional infrastructure and training supports a B++ rating.
Resource Use and Cost Implications
The estimated costs for tarlatamab are significantly higher than existing therapies, raising concerns about affordability and resource burden. The lack of robust evidence for cost offsets further supports a B+ rating.
Evidence Quality and Robustness
The evidence base is primarily derived from a single-arm phase 2 trial, which inherently limits the robustness of the findings. While there are supportive data from phase 3 trials, the lack of direct evidence for the specific population leads to a B++ rating.
Uncertainty, Sensitivity, and Broader Impacts
There is significant uncertainty regarding the comparative effectiveness and cost-effectiveness of tarlatamab, as highlighted by NICE and CDA-AMC. This uncertainty, coupled with the potential for unequal access to treatment, supports a B+ rating.
