Precision oncology – are we at an inflection point?

The paradigm of precision oncology – targeting molecular aberrations rather than traditional histology – is increasingly influencing drug development and clinical trial design. While the approach offers tremendous promise for individualised treatment, it also poses significant challenges for clinical and regulatory landscapes.

One of the most pressing issues in the development and approval of precision therapeutics is treating small, molecularly defined subgroups. Unlike traditional oncology trials that enrol patients based on tumour histology, in fact, precision oncology trials focus on specific genomic alterations irrespective of the tumour's tissue of origin – i.e., in a histology-agnostic manner. For researchers, this means having heterogeneous patient populations across different types of cancer, thus complicating the process of evidence generation.

The development of histology-agnostic drugs raises additional questions for regulatory bodies, requiring new frameworks for benefit-risk assessments. Pan-cancer trials challenge conventional statistical models, as traditional endpoints may not apply uniformly across all tumour types. Regulatory agencies are increasingly required to balance the rapid pace of scientific advancement with the need for robust, reliable evidence, all while considering patient perspectives on the utility of, and accessibility to, new therapies.

In this evolving scenario, collaborative initiatives are essential. The ESMO Translational Research and Precision Medicine Working Group is working towards a framework supporting the design and interpretation of histology-agnostic, biomarker-driven trials, which is an essential step for ensuring robustness in trial results and facilitating regulatory approval.

Precision oncology is at an inflection point. It offers unprecedented opportunities for individualised treatments, but comes with an intricate set of challenges that the scientific and regulatory communities must navigate carefully. As our understanding of cancer's molecular complexity deepens, adapting our research methodologies and regulatory frameworks will be crucial. Collaborative initiatives and dialogue among regulators, clinicians and patients will be instrumental in realising the full potential of precision oncology.