Almost 10 years effort of carrying out a comprehensive genomic profiling in more than 2000 patients with advanced solid tumours within the Copenhagen Prospective Personalized Oncology (CoPPO), a prospective, single-centre, single-arm, open-label study conducted at the Phase I Unit at Department of Oncology, Rigshospitalet, University of Copenhagen, Denmark demonstrated the feasibility of genomic profiling by identifying relevant actionable targets in 57% of patients and by a favourable overall response (OR) in 25% of patients treated with targeted therapy. Notably, the study revealed that ESCAT I/II actionable targets are associated with improved OR, progression-free survival (PFS), and overall survival (OS).
The results underscore the value of genomic profiling for tailored therapy in a Phase I setting and support the ESCAT as a framework for classifying the actionability of molecular alterations according to Dr. Laila Belcaid of the Phase I Unit, Department of Oncology, Rigshospitalet in Copenhagen, Denmark and colleagues, who published the findings on 15 April 2025 in the Annals of Oncology.
The authors wrote in the background that interpreting molecular alterations and selecting targeted therapy remain challenging, as potential targets may become actionable or non-actionable with emerging studies. ESCAT scale aims to bridge the gap between precision cancer medicine and clinical practice by offering a standardised language based on clinical evidence of actionability. This single-centre, non-randomised, open-label prospective study utilised the ESCAT framework and investigated the impact of nearly 10 years of comprehensive genomic profiling for selection of targeted therapy in a Phase I setting.
The study enrolled patients with advanced cancer referred to a Phase I Unit. Fresh tumour tissue was obtained for whole genome or exome sequencing (germline and somatic), RNA sequencing and SNP array. In cases where fresh tumour tissue was unavailable, archived formalin-fixed paraffin-embedded tumour tissue or circulating tumour DNA extracted from plasma were obtained for targeted panels. Genomic reports were reviewed and discussed by a multidisciplinary tumour board and actionable alterations were classified according to the ESCAT. When possible, patients were treated with regimen matched to the genomic profile.
A total of 2147 patients with advanced cancer and exhausted treatment options were enrolled from April 2013 to December 2021. Genomic profiles were obtained in 1866 patients (87%). At least one actionable target was identified in 1062 patients (57%) with a total of 1614 actionable alterations including high RNA CEACAM5 expression (35%), homologous recombination deficiency (HRD) alteration (20%) and tumour mutational burden-high (5%).
Overall, 256 patients, of whom 24% of the patients with an actionable target, were treated with targeted therapy and among these 14 patients were treated with more than one line of targeted therapy. In total, 274 targeted therapy regimens were initiated, and 259 treatments were evaluable with the OR rate of 25% (95% confidence interval 0.20-0.30). ESCAT I/II was associated with improved OR, along with better PFS and OS.
The authors commented that the study aimed to enrol patients in ongoing trials in-house, which expanded from 15 trials in 2013 to nearly three times as many, with changes in both biomarkers used for eligibility and available trials. The results underscore that the ESCAT framework effectively guides targeted therapy selection. Additionally, a significant association was found between the year and patients treated with ESCAT I/II, indicating an increasing trend in the use of treatments with higher actionability.
Reference
Belcaid L, Højgaard M, Tuxen I, et al. Copenhagen Prospective Personalized Oncology (CoPPO) – Impact of comprehensive genomic profiling in more than 2000 patients in a Phase I setting. Annals of Oncology; Published online 15 April 2025. doi: https://doi.org/10.1016/j.annonc.2025.04.004.