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Background/Aim: The costs of new drugs, particularly in oncology, are rising steadily despite various political measures aimed at limiting spending. In Germany alone, spending on patent-protected drugs rose by 18% to around €2.54 billion in the period from February to April 2024 compared with the previous year, with oncology drugs dominating the list of the 40 drug groups with the highest costs. The treatment of cancer therefore represents a resource-intensive area within the healthcare context.

Given these limited financial resources, the question of how to use new and innovative, yet expensive, treatment efficiently is becoming increasingly urgent. This challenge is already recognized within the Germany healthcare context, where the AMNOG (Act of the Reform of the Market for Medicinal Products) mandates an early benefit assessment for newly approved drugs upon market entry. Therefore, cost-effectiveness analyses may serve as an instrument within the reimbursement process should pricing agreements between manufacturers and the statutory health insurance fail to be reached.

Although health economic evaluations are criticised as tools for rationing, we contend that this perspective overlooks the reality of healthcare decision-making under conditions of scarcity. Given that healthcare resources are limited, not only in Germany but worldwide, choices about how these resources are allocated cannot be avoided. Rather than replacing the broader societal and political processes involved in setting healthcare priorities, cost-effectiveness analyses can serve as a valuable source of evidence to inform these decisions, strengthen deliberative processes, and improve transparency of resource allocation.

Determining an appropriate reimbursement price remains a complex and contested process, and the present analysis underscores the value of continued health economic evaluation. As an example of health economic modelling, we therefore selected the addition of pembrolizumab to standard of care for the treatment of locally advanced cervical cancer as an innovative treatment approach, in order to evaluate its cost-effectiveness from the perspective of the German statutory health insurance.

Methods: We constructed a three-state transition model, comprising the health states stable, progressive, and dead. Furthermore, we calculated time-dependent transition probabilities based on published Kaplan-Meier survival data from the respective phase III trials [1].

Transitions were possible from the stable to the progressive state and from both the stable and the progressive state to the dead state. Patients could also remain in their current state. The dead state served as an absorbing state. However, as survival curves represent aggregated multicause data, we had to assume that possible transitions between states would not include a transition back from the progressive to the stable state.

Over a defined time horizon, the model then aggregated costs, life-years, and quality adjusted life-years for both the intervention arm and the standard therapy arm. Based on these, we could calculate the respective incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR).

To evaluate cost-effectiveness, we used a common approach within health economic evaluations, in which one times the GDP per capita in Germany is used as a willingness-to-pay threshold. The calculated ICER and ICUR values had to meet the respective threshold to be considered cost-effective.

Results: Within the baseline scenario, where no parameters were altered from their assumed or calculated values, the addition of pembrolizumab to standard therapy for the treatment of locally advanced cervical cancer could not be considered cost-effective. This result is supported by the deterministic and probabilistic sensitivity analyses. The deterministic sensitivity analysis showed that the drug price had the greatest influence on the ICUR, and that a price reduction about 86.0% would be needed to achieve cost-effectiveness. The probabilistic sensitivity analysis showed a probability of only 0.6% of achieving cost-effectiveness against the assumed willingness-to-pay-threshold.

Discussion/Conclusion: Two other health economic evaluations assessed the treatment from an international perspective [2], [3]. One evaluation focused solely on the US healthcare system and concluded that the treatment was not cost-effective [2]. The second one assessed the US, Italian, and Chinese settings, concluding that the treatment was cost-effective in the US and Chinese setting but not in the Italian setting [3].

Two of the main differences were the applied time horizon and the utility values assigned to the different health states across the two intervention arms.

While all analyses concluded that drug costs are the most influential parameter with the respect to cost-effectiveness, in our view a substantial reduction in drugs costs would be necessary for the treatment to be considered cost-effective within the German healthcare context.

Based on the conflicting results from external studies and our own analyses, we conclude that further research is needed. This highlights the need for more transparent and standardized health economic evaluations across different healthcare settings to provide a more comprehensive evidence base and complete the current research perspective.

Literatur

[1] Lorusso D, Xiang Y, Hasegawa K, Scambia G, Leiva M, Ramos-Elias P, Acevedo A, Sukhin V, Cloven N, Pereira de Santana Gomes AJ, Contreras Mejía F, Reiss A, Ayhan A, Lee JY, Saevets V, Zagouri F, Gilbert L, Sehouli J, Tharavichitkul E, Lindemann K, Lazzari R, Chang CL, Lampé R, Zhu H, Oaknin A, Christiaens M, Polterauer S, Usami T, Li K, Yamada K, Toker S, Keefe SM, Pignata S, Duska LR; ENGOT-cx11/GOG-3047/KEYNOTE-A18 investigators. Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): a randomised, double-blind, phase 3 clinical trial. Lancet. 2024 Apr 6;403(10434):1341-1350. DOI: 10.1016/S0140-6736(24)00317-9
[2] Courtney PT, Venkat PS, Shih YT, Chang AJ, Lee A, Steinberg ML, Raldow AC. Cost-Effectiveness of Pembrolizumab With Chemoradiotherapy for Locally Advanced Cervical Cancer. JAMA Netw Open. 2025 Mar 3;8(3):e250033. DOI: 10.1001/jamanetworkopen.2025.0033
[3] Liu K, Zhu Y, Zhu H. International cost-effectiveness analysis of chemoradiotherapy plus pembrolizumab for locally advanced cervical cancer. J Gynecol Oncol. 2025 Nov;36(6):e106. DOI: 10.3802/jgo.2025.36.e106