Genomic actionability and matched targeted therapy in a decade-long institutional precision medicine program for solid tumors

Abstract

Actionability; Matched therapies; Molecular trials

Accionabilitat; Teràpies emparellades; Assaigs moleculars

Accionabilidad; Terapias emparejadas; Ensayos moleculares

ackground: Precision oncology has evolved from concept to clinical reality, advancing cancer treatment and drug development in the last decade. However, disparities persist in patient access to comprehensive genomic profiling and matched therapies. Materials and methods: This was a retrospective analysis of all patients enrolled in the Vall d'Hebron Institute of Oncology (VHIO) precision medicine program (PMP) between 2014 and 2024. Tumor profiling outcomes were reviewed, focusing on actionable alterations, classified by the European Society for Medical Oncology Scale for Clinical Actionability of Molecular Targets (ESCAT). Interpretation and therapy prioritization were standardized through regular multidisciplinary molecular tumor boards. Key performance indicators (KPIs) included the proportions of patients with ESCAT tier I-IV alterations and those receiving matched therapies, either via clinical trials or approved regimens. The analysis also considered advances in molecular diagnostics, such as liquid biopsies, and the evolving clinical trial portfolio requiring biomarkers. Results: From 2014 to 2024, 12 168 unique patients underwent 13 718 multi-gene molecular profiles at VHIO PMP. The detection rate of actionable alterations increased substantially over time, from 10.1% in 2014 to 53.1% in 2024, paralleling advances in drug biomarkers, sequencing technology, and broader use of assays. Overall, 10.1% of patients received molecularly matched therapies, rising from 1% in 2014 to 14.2% in 2024. Among patients with actionable alterations, 23.5% received targeted therapies, with annual rates ranging from 19.5% to 32.7%. Liquid biopsy integration notably enhanced actionable target detection and therapy access. The proportion of clinical trials with molecular inclusion criteria varied, starting at 40.2% in 2014 and dropping to 19.4% in 2020 before rising to 34.2% in 2024. Conclusion: Over a decade, VHIO's institutionally integrated PMP has enabled robust actionable alteration detection and access to matched therapies. Standardized KPI monitoring enables ongoing evaluation and sustainability of program performance. Continued innovation in diagnostics and molecularly guided trials is essential for further progress in precision oncology.

This work was supported by the Fero Foundation (no grant number) (Advanced Molecular Diagnostics Program—DIAMAV), ‘la Caixa’ Foundation (CaixaResearch Advanced Oncology Research Program) and the Fundación CRIS Contra el Cáncer (VHIO-CRIS Program for Precision Oncology and Digitalization).