# Assessing the Impact of Comprehensive Genomic Profiling on Therapeutic Selection for Advanced Solid Tumors in Portugal

## TL;DR

This study shows that genomic profiling helps guide treatment and improve outcomes for patients with advanced solid tumors in Portugal.

## Contribution

The study provides real-world evidence of CGP's clinical impact in a Portuguese population with advanced solid tumors.

## Key findings

- Actionable genomic alterations were identified in 50.7% of patients.
- CGP results influenced treatment decisions in 24.4% of patients.
- Approximately 14.6% of patients achieved disease control at 16 weeks with CGP-guided therapy.

## Abstract

Real-world evidence data on the clinical impact of comprehensive genomic profiling (CGP) remains limited. The FRONTAL study, a multicenter national registry in Portugal, evaluated the use of CGP in patients with advanced solid tumors who underwent testing with FoundationOne CDx, Liquid CDx, or FoundationOne Heme. Among 205 patients enrolled between 2020 and 2025, actionable genomic alterations were identified in half of the cases, and CGP results influenced treatment decisions in about one-quarter of patients. Importantly, approximately 15% of the total cohort achieved disease control at 16 weeks following CGP-guided therapy. Overall, this study provided real-world evidence supporting the clinical relevance of CGP in informing treatment strategies for advanced solid tumors in Portugal.

Background: Comprehensive genomic profiling (CGP) is a tool used in precision oncology to identify genomic alterations and match them with targeted therapies across several tumor types. However, real-world data on its clinical utility and impact remains limited. The FRONTAL study (Foundation Medicine Real wOrld evideNce in porTugAL) is a multicenter academic initiative that established a national registry of Portuguese patients with solid tumors who underwent CGP with FoundationOne CDx, Liquid CDx or FoundationOne Heme assays. Methods: Eligible patients had advanced solid tumors not suitable for curative treatment at the time of recruitment. Prior CGP testing was permitted if taken within 12 months before study initiation. Genomic profiling data were extracted from FoundationOne Medicine reports, and clinical information was extracted from medical records. Actionable alterations were defined as those associated with approved treatments or with clinical evidence of benefit in other cancers, per NCCN guidelines. Variant interpretation was also reviewed according to ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) guidelines. The primary outcome was disease control at 16 weeks, defined by the absence of progression. Results: The study included 205 patients between 2020 and 2025 across 10 sites, with colorectal (40, 19.5%), sarcomas (28, 13.7%), and other gastrointestinal tumors (22, 10.7%) being the most common pathologies. Actionable alterations were identified in 104 cases (50.7%). Genomic findings guided therapy decisions in 50 patients (24.4%), of whom 30 achieved disease control at 16 weeks (14.6%). Conclusions: The FRONTAL study highlighted the clinical relevance of CGP in advanced solid tumors. Over half of the patients had actionable alterations, a quarter had therapy changes based on CGP results, and improved disease outcome was observed in approximately 15% of the cohort.