Drug repurposing and treatment optimisation in oncology: regulatory challenges and policy priorities

Drug repurposing and treatment optimisation are increasingly important strategies to improve cancer outcomes by making better use of existing therapies. Drug repurposing involves identifying new clinical indications for approved or abandoned medicines, while treatment optimisation focuses on refining how established therapies are used within their licensed indications, for example, through dose, duration, or sequencing modifications. Although both approaches aim to maximise patient benefit and are supported by extensive clinical experience, they face distinct and shared regulatory challenges. We examine why current regulatory and legislative frameworks remain poorly aligned with the objectives, risk profiles, and evidentiary needs of drug repurposing and treatment optimisation studies. Drawing on illustrative case studies in oncology, including aspirin and metformin repurposing, immunotherapy optimisation, and regulatory initiatives such as Project Optimus, we demonstrate how regulatory systems designed primarily for de novo drug development create disproportionate burdens, delay evidence generation, and impede translation into routine clinical practice. The heterogeneity of evidence across prevention and treatment settings, the absence of clear licensing pathways for off-patent medicines, and the limited integration of optimisation into post-authorisation management are recurring themes. This review highlights how regulatory bottlenecks arise across the trial life cycle and how diverse treatment optimisation study designs could better address patient-centred outcomes. We propose that proportionate regulatory frameworks encompassing marketing authorisation, post-authorisation evidence generation, and reimbursement mechanisms are necessary to enable the efficient evaluation, regulatory approval, and sustainable implementation of repurposed and treatment-optimised therapies. Aligning regulation with real-world cancer care requires coordinated action from regulators, policymakers, academia, industry and clinicians to ensure that established medicines are not only approved, but used optimally to deliver meaningful, evidence-based benefit.