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Updated: Dec 18, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Clinical Impact of Plasma and Tissue Next-Generation Sequencing in Advanced Non-Small Cell Lung Cancer: A Real-World
Laura Bonanno1, Alberto Pavan1, Alessandra Ferro1,2
1Medical Oncology 2, Istituto Oncologico Veneto (IOV)-Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padova, Italy.
Background:
Targeted agents have improved the outcome of a subset of non-small cell lung cancer (NSCLC). Molecular profiling by next-generation sequencing (NGS) allows screening for multiple genetic alterations both in tissue and in plasma, but limited data are available concerning its feasibility and impact in real-world clinical practice.
Methods:
Patients with advanced NSCLC consecutively referring to our Institution for potential eligibility to VISION trial (NCT02864992) were prospectively enrolled. They were already screened with standard method, and EGFR/ALK/ROS-1 positive cases were excluded. NGS was performed in plasma and tissue using the Guardant360 test covering 73 genes and the Oncomine Focus Assay covering 59 genes, respectively.
Results:
The study included 235 patients. NGS was performed in plasma in 209 (88.9%) cases; 78 of these (37.3%) were evaluated also in tissue; tissue only was analyzed in 26 cases (11.1%). Half of the tissue samples were deemed not evaluable. Druggable alterations were detected in 13 (25%) out of 52 evaluable samples and 31 of 209 (14.8%) of plasma samples. Improved outcome was observed for patients with druggable alterations if treated with matched targeted agents: they had a longer median overall survival (not reached) compared with the ones who did not start any targeted therapy (9.1 months; 95% confidence interval, 4.6-13.6; p = .046). The results of NGS testing potentially also affected the outcome of patients treated with immunotherapy.
Conclusion:
Systematic real-life NGS testing showed the limit of tissue analysis in NSCLC and highlighted the potentiality of genetic characterization in plasma in increasing the number of patients who may benefit from NGS screening, both influencing the clinical decision-making process and affecting treatment outcome.
Implications For Practice:
Genetic characterization of cancer has become more important with time, having had positive implications for treatment specificity and efficacy. Such analyses changed the natural history of advanced non-small cell lung cancer (aNSCLC) with the introduction of drugs targeted to specific gene alterations (e.g., EGFR mutations, ALK and ROS-1 rearrangements). In the field of cancer molecular characterization, the applicability of the analysis of a wide panel of genes using a high-throughput sequencing approach, such as next-generation sequencing (NGS), is still a matter of research. This study used NGS in a real-world setting to systematically and prospectively profile patients with aNSCLC. The aim was to evaluate its feasibility and reliability, as well as consequent access to targeted agents and impact on clinical outcome whenever a druggable alteration was detected either in tumor tissue samples or through liquid biopsy.
Insights
Next-generation sequencing (NGS) in real-world non-small cell lung cancer (NSCLC) identified druggable alterations in plasma, improving patient outcomes with targeted therapies. This molecular profiling demonstrated the potential of liquid biopsies for broader patient benefit.
Area of Science:
- Oncology
- Genomics
- Translational Research
Background:
- Targeted therapies have improved outcomes for specific non-small cell lung cancer (NSCLC) patient subsets.
- Molecular profiling using next-generation sequencing (NGS) can identify genetic alterations in both tissue and plasma.
- Limited data exist on the real-world feasibility and impact of NGS in clinical practice for NSCLC.
Purpose of the Study:
- To evaluate the feasibility and reliability of systematic, real-world NGS testing in advanced NSCLC patients.
- To assess the impact of NGS on identifying druggable alterations and subsequent targeted therapy eligibility.
- To determine the influence of NGS-driven molecular characterization on clinical decision-making and patient outcomes.
Main Methods:
- Prospective enrollment of advanced NSCLC patients undergoing screening for the VISION trial.
- Exclusion of EGFR/ALK/ROS-1 positive cases identified by standard methods.
- NGS analysis of plasma (Guardant360) and tissue (Oncomine Focus Assay) for genetic alterations.
Main Results:
- NGS was performed in plasma for 209 patients (88.9%) and in tissue for 78 (37.3%); half of tissue samples were not evaluable.
- Druggable alterations were found in 25% of evaluable tissue samples and 14.8% of plasma samples.
- Patients with detected druggable alterations who received matched targeted therapy showed significantly longer overall survival (not reached vs. 9.1 months).
Conclusions:
- Real-world NGS testing highlights limitations of tissue analysis and the potential of plasma-based liquid biopsies in NSCLC.
- Genetic characterization via NGS increases the number of patients eligible for targeted therapies and influences treatment decisions.
- NGS screening in NSCLC impacts clinical decision-making and improves patient treatment outcomes.
