Oncology drug development is largely driven by clinical trials designed to secure rapid regulatory approval through demonstration of efficacy and safety in defined populations. While these trials underpin benefit–risk assessments for marketing authorisation, they frequently leave unresolved questions about optimal dose, duration, schedule, sequencing and combinations in routine practice. Medicines may therefore reach the market without comprehensive evidence on their most efficient and patient-centred use. At the same time, global cancer incidence and prevalence continue to rise, with the World Health Organization forecasting a 50% increase in global cancer incidence by 2040. Advances in detection and treatment have increased the number of people living with cancer or long-term treatment effects, while escalating costs of innovative systemic therapies exert sustained pressure on healthcare systems. Treatment optimisation research has emerged as a response to these clinical and economic challenges, aiming to generate actionable evidence that supports informed decision-making and more sustainable allocation of resources.
Gaps in Incentives and Funding
Stakeholders within the Cancer Medicines Forum have highlighted structural shortcomings in the current research framework. In the pre-authorisation setting, incentives focus primarily on expedited development and early access for patients with high unmet need. Refinement of treatment parameters such as dose adjustments, schedule modifications or sequencing strategies receives comparatively limited attention. As a result, anticancer therapies may be approved while important optimisation questions remain unanswered.
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In the post-authorisation phase, academia is often well positioned to address uncertainties emerging from routine clinical practice. However, the absence of a dedicated international framework and structured incentives for collaboration between academia and industry constrains progress. Funding remains a major barrier. Optimisation studies typically require large sample sizes and prolonged follow-up, yet funding opportunities are limited. Comparative effectiveness research, particularly when addressing clinically relevant issues such as treatment de-escalation, struggles to secure sustained financial support. Although European Union initiatives under the Cancer Mission support pragmatic clinical trials, a comprehensive funding framework for systematic public health-oriented academic oncology research is still lacking.
Regulatory, Recruitment and Implementation Challenges
Regulatory and legal complexities further impede optimisation research. Trials investigating modified use of authorised medicines are frequently subject to the same requirements as studies of new investigational products. The low-intervention clinical trial category introduced under Regulation (EU) No. 536/2014 was intended to facilitate certain trials involving authorised products. However, many optimisation studies do not qualify for this designation. Administrative burdens, variability in implementation and limited procedural simplifications continue to hinder efficient conduct.
Recruitment presents additional challenges. Trials evaluating adjustments to established therapies may appear less attractive than studies of novel agents. When medicines are accessible through early access schemes or reimbursement decisions, enrolment can be particularly difficult. The absence of structured mechanisms to facilitate international collaboration often leads to nationally conducted trials, limiting recruitment potential and reducing research efficiency. Ethical considerations are especially relevant in de-escalation studies aimed at reducing treatment intensity. Although the objective is to minimise toxicity and enhance quality of life while maintaining efficacy, concerns about potential under-treatment in life-threatening diseases may arise.
Even when optimisation evidence is generated, integration into routine practice may be limited. Post-authorisation findings are not always submitted for regulatory reassessment, as label updates remain at the discretion of marketing authorisation holders. Approved indications strongly influence health technology assessment, pricing and reimbursement decisions. Optimisation results suggesting modifications to established regimens may therefore encounter reimbursement complexity and limited uptake.
Roadmap for Systematic Integration
To address these barriers, stakeholders have proposed a structured roadmap for systematic integration of treatment optimisation into oncology research. Recognition of optimisation as a societal and public health priority has been emphasised, alongside adaptation of legal frameworks to incorporate optimisation in both pre- and post-authorisation processes. Coherent implementation across European Union and national authorities is considered essential.
Regulatory agencies are encouraged to integrate optimisation considerations into established processes such as scientific advice and protocol assistance. The announced revision of the European Medicines Agency anticancer guideline and the ongoing reform of European pharmaceutical legislation represent opportunities to embed optimisation more explicitly within regulatory pathways. In the post-authorisation setting, stakeholders have called for a dedicated European framework to address optimisation questions not incorporated into initial development programmes, fostering international cooperation and multistakeholder engagement.
Expansion of funding mechanisms for academic-led, patient-centred trials has also been highlighted. National initiatives in Member States such as Belgium and the Netherlands illustrate potential models for publicly funded, practice-oriented clinical research. Adaptive and risk-proportionate regulatory approaches, along with improved coordination between regulatory frameworks governing clinical trials, in vitro diagnostics and health technology assessment, are viewed as necessary to reduce administrative burden and support cross-border collaboration.
Patient involvement is positioned as central to successful optimisation research. Active engagement of patients and patient organisations can inform research priorities, study design and outcome selection, ensuring alignment with outcomes such as symptom relief, quality of life and functional status.
Treatment optimisation in oncology remains underdeveloped despite its potential to improve patient outcomes and support sustainability of healthcare systems. Barriers span incentives, funding limitations, regulatory complexity, recruitment challenges and difficulties in translating findings into practice. Through multistakeholder dialogue, the Cancer Medicines Forum has articulated strategic recommendations aimed at embedding optimisation research within existing regulatory, clinical and funding structures. Systematic integration of these measures may strengthen evidence generation, inform clinical decision-making and contribute to a more sustainable and patient-centred approach to cancer care.
Source: Journal of Cancer Policy
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