Copenhagen Prospective Personalized Oncology (CoPPO)-impact of comprehensive genomic profiling in more than 2000 patients in a phase I setting

Abstract

Background: Targeted therapy based on the molecular characterization of tumors has been among the most remarkable advances in cancer medicine. In this article, we report the impact of almost 10 years of comprehensive genomic profiling in >2000 patients with advanced solid tumors at the Phase I Unit, Department of Oncology, Rigshospitalet, Copenhagen, Denmark.

Materials and methods: A prospective, single-center, single-arm open-label study (NCT02290522) was conducted, enrolling patients with advanced cancer referred to a phase I unit. Fresh tumor tissue was obtained for whole-genome or -exome sequencing (germline and somatic), RNA sequencing, and single nucleotide polymorphism (SNP) array. In cases where fresh tumor tissue was unavailable, archived formalin-fixed paraffin-embedded tumor tissue or circulating tumor DNA extracted from plasma were obtained for targeted panels. Genomic reports were reviewed and discussed by a multidisciplinary tumor board and actionable alterations were classified according to the European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets (ESCAT). When possible, patients were treated with regimen matched to the genomic profile.

Results: 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 (n = 559, 35%), homologous recombination deficiency (HRD) alteration (n = 314, 20%), and tumor mutational burden-high (n = 84, 5%). Overall, 256 patients (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 treatment regimens were initiated, and 259 treatments were evaluable with an overall response (OR) rate of 25% (95% confidence interval 0.20% to 0.30%). ESCAT I/II was associated with improved OR, along with better progression-free survival (PFS) and overall survival (OS).

Conclusion: This large-scale study demonstrates that genomic profiling is efficient in identifying actionable targets and in matching patients to targeted therapies.

Keywords: ESCAT; genomic profile; phase I; targeted therapy.