Biomarker testing implementation for molecularly targeted therapy in non-small cell lung cancer patients

Tumori. 2025 Aug;111(4):293-301. doi: 10.1177/03008916251341996. Epub 2025 Jul 10.

Abstract

Background: Recent advancements in identifying druggable molecular drivers in lung adenocarcinoma (LUAD), have transformed treatment paradigms. In recent years, Next Generation Sequencing (NGS) has gained momentum as an essential tool for in-depth simultaneous analysis of multiple genes, thereby streamlining the diagnostic process in LUAD. Despite this, the implementation of NGS testing in both the US and Europe remains suboptimal.

Aims: In compliance with a decree issued by the Italian Ministry of Health, Lombardy Region recently launched an initiative to implement NGS testing in patients with advanced LUAD. In this context, a real-world prospective observational study was planned to assess the efficacy of the regional network of molecular laboratories in testing nine biomarkers (KRAS p.G12C, EGFR, BRAF, HER2, MET mutations; ALK, ROS1, NTRK1-3, RET rearrangements), for on-label molecularly targeted drugs.

Results: In 2023, out of the 2784 advanced/metastatic LUAD patients expected in Lombardy, 2343 (84.2%) were successfully evaluated with an NGS panel including all the nine biomarkers for on-label drugs. Actionable aberrations were identified in 45.5% of the patients (1068/2343), predominantly involving EGFR, KRAS, and ALK genes.

Conclusion: Our data provide evidence that establishing a structured network of NGS hubs is mandatory to ensure access of advanced LUAD patients to molecularly targeted treatments.

Keywords: Lung adenocarcinoma; NGS; precision oncology; target therapy.

Publication types

  • Observational Study

MeSH terms

  • Adenocarcinoma of Lung / drug therapy
  • Adenocarcinoma of Lung / genetics
  • Aged
  • Anaplastic Lymphoma Kinase / genetics
  • Biomarkers, Tumor* / genetics
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Erb-b2 Receptor Tyrosine Kinases / genetics
  • ErbB Receptors / genetics
  • Female
  • High-Throughput Nucleotide Sequencing / methods
  • Humans
  • Italy
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Male
  • Middle Aged
  • Molecular Targeted Therapy* / methods
  • Mutation
  • Prospective Studies
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins p21(ras) / genetics

Substances

  • Biomarkers, Tumor
  • Anaplastic Lymphoma Kinase
  • ErbB Receptors
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)
  • Erb-b2 Receptor Tyrosine Kinases
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins
  • ALK protein, human
  • ROS1 protein, human