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Updated: Sep 3, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Upfront Next Generation Sequencing in Non-Small Cell Lung Cancer
Shelley Kuang1, Andrea S Fung1, Kirstin A Perdrizet1
1Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON M5G 2M9, Canada.
Abstract:
In advanced non-small cell lung cancer (NSCLC), patients with actionable genomic alterations may derive additional clinical benefit from targeted treatment compared to cytotoxic chemotherapy. Current guidelines recommend extensive testing with next generation sequencing (NGS) panels. We investigated the impact of using a targeted NGS panel (TruSight Tumor 15, Illumina) as reflex testing for NSCLC samples at a single institution. Molecular analysis examined 15 genes for hotspot mutation variants, including AKT1, BRAF, EGFR, ERBB2, FOXL2, GNA11, GNAQ, KIT, KRAS, MET, NRAS, PDGFRA, PIK3CA, RET and TP53 genes. Between February 2017 and October 2020, 1460 samples from 1395 patients were analyzed. 1201 patients (86.1%) had at least one variant identified, most frequently TP53 (47.5%), KRAS (32.2%) or EGFR (24.2%). Among these, 994 patients (71.3%) had clinically relevant variants eligible for treatment with approved therapies or clinical trial enrollment. The incremental cost of NGS beyond single gene testing (EGFR, ALK) was CAD $233 per case. Reflex upfront NGS identified at least one actionable variant in more than 70% of patients with NSCLC, with minimal increase in testing cost. Implementation of NGS panels remains essential as treatment paradigms continue to evolve.
Insights
Reflex upfront next-generation sequencing (NGS) panels in non-small cell lung cancer (NSCLC) identified actionable genomic alterations in over 70% of patients, proving essential for evolving treatment strategies with minimal cost increase.
Area of Science:
- Oncology
- Genomics
- Molecular Diagnostics
Background:
- Advanced non-small cell lung cancer (NSCLC) treatment benefits from targeted therapies for patients with actionable genomic alterations.
- Current guidelines advocate for extensive next-generation sequencing (NGS) panel testing for NSCLC.
- The study evaluates the utility of a targeted NGS panel as reflex testing in a clinical setting.
Purpose of the Study:
- To assess the impact and yield of a targeted NGS panel for reflex testing in NSCLC.
- To determine the frequency of actionable genomic alterations identified by NGS in NSCLC patients.
- To evaluate the cost-effectiveness of implementing NGS panels for NSCLC molecular profiling.
Main Methods:
- A targeted NGS panel (TruSight Tumor 15, Illumina) was used for reflex testing on 1460 NSCLC samples from 1395 patients (February 2017 - October 2020).
- The panel analyzed 15 genes for hotspot mutation variants.
- Molecular analysis results were correlated with treatment eligibility for approved therapies or clinical trials.
Main Results:
- 1201 patients (86.1%) had at least one variant identified, with TP53 (47.5%), KRAS (32.2%), and EGFR (24.2%) being most frequent.
- 994 patients (71.3%) harbored clinically relevant variants actionable by approved therapies or clinical trials.
- The incremental cost of NGS reflex testing was CAD $233 per case.
Conclusions:
- Reflex upfront NGS testing in NSCLC identifies actionable variants in over 70% of patients.
- This approach is essential for guiding personalized treatment strategies in NSCLC.
- The implementation of NGS panels offers a cost-effective solution for molecular profiling in NSCLC.
