Tissue- and liquid-biopsy based NGS profiling in advanced non-small-cell lung cancer in a real-world setting: the IMMINENT study

Marco Sposito ¹, Lorenzo Belluomini ¹, Riccardo Nocini ²

¹Section of Innovation Biomedicine - Oncology Area, Department of Engineering for Innovation Medicine (DIMI), University of Verona and University and Hospital Trust/Azienda Ospedaliero-Universitaria Integrata (AOUI), Verona, Italy.
²Otolaryngology-Head and Neck Surgery Department, University of Verona Hospital Trust, Verona, Italy.
³Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy.
⁴Medical Oncology Unit, Azienda Ospedaliera (AO) San Giovanni Addolorata Hospital, Rome, Italy.
⁵Medical Oncology Unit, San Giuseppe Moscati Hospital, Taranto, Italy.
⁶Section of Oncology, Azienda Ospedaliera (AO) Ospedali Riuniti "Villa Sofia- V. Cervello", Palermo, Italy.
⁷Department of Clinical Oncology, San Bortolo General Hospital, Azienda ULSS8 Berica, Vicenza, Italy.
⁸Department of Experimental Medicine, Sapienza University, Rome, Italy.
⁹Medical Oncology Department, Fondazione Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale Dei Tumori, Milan, Italy.
¹⁰Division of Medical Oncology B, Policlinico Umberto I, Rome, Italy.
¹¹Medical Oncology Department, Santa Chiara Hospital, Trento, Italy.
¹²Lung Unit, Ospedale Pederzoli, Peschiera del Garda, Verona, Italy.
¹³Medical Oncology, Azienda Ospedaliero Universitaria Policlinico "G. Rodolico-S. Marco", Catania, Italy.
¹⁴Department of Medical Oncology, Unità Operativa Complessa (UOC) Oncologia, Taormina, Italy.
¹⁵Medical Oncology Unit, San Giovanni di Dio e Ruggi d'Aragona, Salerno, Italy.
¹⁶AdRes Health Economics and Outcome Research, Turin, Italy.
¹⁷Roche S.p.A., Monza, Italy.
¹⁸Department of Public Health, University Federico II of Naples, Naples, Italy.
¹⁹Department of Oncology, San Luigi Gonzaga Hospital, University of Turin, Orbassano, Italy.
²⁰Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Roma, Italy.
²¹Medical Oncology, Università Cattolica del Sacro Cuore, Roma, Italy.

⁰Section of Innovation Biomedicine - Oncology Area, Department of Engineering for Innovation Medicine (DIMI), University of Verona and University and Hospital Trust/Azienda Ospedaliero-Universitaria Integrata (AOUI), Verona, Italy.

Frontiers in Oncology +

|

July 24, 2024

View abstract on PubMed

Summary

Comprehensive genomic profiling using next-generation sequencing (NGS) in advanced non-small cell lung cancer (NSCLC) reveals frequent gene alterations and provides valuable prognostic insights. Testing at initial diagnosis improves survival probabilities.

Area Of Science

Oncology
Genomics
Molecular Diagnostics

Background

Testing for driver alterations is crucial for identifying actionable therapeutic targets in non-small cell lung cancer (NSCLC).
Comprehensive genomic profiling (CGP) using next-generation sequencing (NGS) is increasingly important in clinical practice for advanced NSCLC.

Purpose Of The Study

To assess the distribution and real-world frequency of gene alterations in advanced NSCLC.
To correlate gene alterations with patient characteristics using NGS-based profiling.
To evaluate the outcomes of FoundationOne (F1CDx) and FoundationLiquid CDx (F1L/F1LCDx) in a nationwide initiative.

Main Methods

Utilized F1CDx (324 genes) for tissue samples and F1L (70 genes) or F1LCDx (324 genes) for liquid biopsies.
Analyzed data from 232 advanced NSCLC patients across 11 institutions.
Investigated gene alterations, tumor mutational burden (TMB), and overall survival (OS).

Main Results

Found alterations in 170 genes, with TP53 (58%), KRAS (22%), CDKN2A/B (19%), and STK11 (17%) being most frequent.
Actionability rates were comparable between tissue (36.2%) and liquid (34%) NGS assays.
Higher TMB was observed in smokers, and patients with ≥3 gene mutations had significantly lower median OS.

Conclusions

NGS-based molecular profiling of advanced NSCLC, using either tissue or blood samples, provides significant predictive and prognostic information.
Early genomic profiling at diagnosis correlates with improved conditional three-year survival probabilities.

Keywords:

liquid biopsy next generation sequencing non-small cell lung cancer precision medicine target therapy