What payers will ask
Is the clinical benefit the kind payers reward? — Clinical effectiveness
The clinical effectiveness of tarlatamab is based on the DeLLphi-301 trial, which showed an objective response rate (ORR) of 40.4% and a median overall survival (OS) of 14.3 months. However, the trial did not directly compare tarlatamab with chemotherapy, leading to uncertainties in the clinical benefit. The indirect treatment comparison (ITC) results are also uncertain due to the unanchored nature of the analysis, which raises concerns about the robustness of the efficacy claims.
Does the economic case hold at the expected price? — Cost effectiveness
The cost-effectiveness estimates for tarlatamab are above the acceptable range for NHS resources, with ICERs reported at £35,393 per QALY gained. The committee expressed concerns about the uncertainties in the cost-effectiveness model, particularly regarding the extrapolation of survival data and the utility values used. This raises questions about the overall value proposition of tarlatamab.
Is there quality-of-life evidence payers weigh? — Quality of life
The evidence regarding HRQoL is limited, with utility values derived from the DeLLphi-301 trial. While the committee noted that these values may be higher than expected for the population with extensive-stage small-cell lung cancer (ES-SCLC), it concluded that the quality of life for patients in clinical practice is unknown. The committee preferred to use the utility values from the MAIC-adjusted population, but the overall impact on HRQoL remains uncertain.
Does the safety profile hold up for payers? — Safety and Adverse Effects
Tarlatamab has a notable safety profile, with serious adverse effects such as cytokine release syndrome (CRS) reported in 50% of patients and immune effector cell-associated neurotoxicity syndrome (ICANS) in 7%. While these events can be serious, they are manageable with appropriate monitoring and treatment. The committee acknowledged the need for healthcare staff training to manage these adverse effects, indicating a generally good tolerability.
Was the drug compared against what payers expect? — Comparator Selection
The only relevant comparator for tarlatamab is chemotherapy, as best supportive care is not considered a valid comparator. However, the lack of direct comparison with chemotherapy and reliance on indirect treatment comparisons introduces significant uncertainty in the evidence base. The committee noted that the ITC results were not fully reliable due to the unanchored nature of the analysis.
Is the population defined the way payers need it? — Patient Population and Subgroups
The trial population in the DeLLphi-301 study included patients with an ECOG status of 0 or 1, which aligns with the expected population for tarlatamab in clinical practice. However, the committee noted that the treatment is only suitable for a specific subgroup of patients, which may limit generalizability. Overall, the population is moderately representative of those who would receive tarlatamab.
Does the drug fit how care is delivered and paid for? — Care Pathway Integration
Integrating tarlatamab into existing care pathways may require significant adjustments, including additional monitoring and training for healthcare professionals. The committee noted that the treatment would necessitate hospital admissions for monitoring, which could disrupt existing pathways. This indicates a high level of disruption to current practices.
Are the wider system costs understood? — Resource Use and Cost Implications
The budget impact of tarlatamab is concerning, with high costs associated with the treatment and monitoring of adverse effects. The committee noted that the ICERs were above acceptable thresholds, indicating a significant resource burden. This raises concerns about the affordability of tarlatamab within the NHS.
Would the evidence survive payer scrutiny? — Evidence Quality and Robustness
The evidence base for tarlatamab is primarily derived from the DeLLphi-301 trial, which has limitations due to its uncontrolled design and reliance on indirect comparisons. The committee expressed concerns about the robustness of the evidence, particularly regarding the uncertainties in the ITC and the extrapolation of survival data. This indicates moderate quality evidence with significant gaps.
How exposed is the case to uncertainty? — Uncertainty, Sensitivity, and Broader Impacts
There is a high level of uncertainty surrounding the clinical effectiveness and cost-effectiveness of tarlatamab, particularly due to the reliance on indirect treatment comparisons and the extrapolation of survival data. The committee noted that the uncertainties could impact decision-making and the potential for broader societal implications, such as equity in access to treatment.
