The German Federal Joint Committee (G-BA) has approved a new indication for Pembrolizumab Enfortumab therapy in combination with Enfortumab Vedotin as a first-line treatment for adult patients with unresectable or metastatic urothelial carcinoma. This decision is based on a structured benefit assessment comparing this therapy to standard treatments. It focuses on patients’ eligibility for cisplatin-based regimens. For those ineligible for either cisplatin or carboplatin, no additional benefit was found.

Clinical Effectiveness Overview

• Mortality Benefits: In cisplatin-eligible patients, the combination therapy showed a mortality benefit but lacked quantifiable superiority over cisplatin/gemcitabine. For carboplatin-eligible patients, it demonstrated significant mortality improvement compared to carboplatin/gemcitabine, along with symptomatic benefits like reduced nausea and constipation. However, for patients ineligible for both, no efficacy was shown over alternatives like Atezolizumab monotherapy or best supportive care.

Economic Aspects

• Cost Implications: The annual treatment costs for Pembrolizumab Enfortumab therapy are much higher than standard therapies, estimated at €181,464 per patient. Standard options include carboplatin, and gemcitabine, or maintenance therapy with avelumab, depending on the regimen and patient subgroup.

Safety Profile and Adverse Events

• Benefits and Risks: The combination therapy has advantages, such as fewer severe adverse effects, and risks, including immune-related side effects like severe hyperglycemia.

Regulatory and Assessment Framework

The G-BA conducts early benefit assessments under the Arzneimittelmarkt-Neuordnungsgesetz (AMNOG). This process compares new therapies against existing standards to ensure efficient resource use in Germany’s statutory health insurance (GKV) system. Pembrolizumab is a PD-1 checkpoint inhibitor, while Enfortumab Vedotin is an antibody-drug conjugate targeting Nectin-4.

Implications for Healthcare Economics and Access

1. Healthcare Economics: The high cost of Pembrolizumab Enfortumab therapy raises affordability concerns. Its benefits for some subpopulations may limit widespread use.
2. Reimbursement Challenges: High costs and limited evidence for certain groups may hinder reimbursement. Price negotiations with GKV payers could lead to reductions.
3. Addressing Unmet Needs: The lack of benefits for cisplatin- and carboplatin-ineligible patients highlights the need for alternative treatments. More research could improve outcomes.

Final Reflections

The G-BA’s decision reflects a tailored approach to clinical effectiveness. While Pembrolizumab Enfortumab therapy shows promise for select groups, its high costs and selective effectiveness emphasize the need for precision medicine and cost containment. For details, see the G-BA’s official assessment.