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Genetic Testing in Non-Small Cell Lung Cancer - Clinical Practice Experience

30. 9. 2020

Targeted therapy has brought significant improvements to certain groups of patients with non-small cell lung cancer (NSCLC). Selecting patients who will benefit from targeted therapy can be performed using molecular profiling with next-generation sequencing (NGS) techniques. However, we still lack sufficient data on the feasibility and results of such profiling in real-world clinical practice, which was the focus of an analysis recently published in The Oncologist.

Genetic Testing and Cancer Treatment

The availability of targeted therapy has significantly transformed diagnostic and therapeutic algorithms in solid tumors, especially in the case of advanced NSCLC. Until recently, most information necessary for deploying targeted therapy was obtained through tests for individual specific genomic alterations. However, advancements in molecular genetics have now made it possible to perform genetic screening of an entire panel of mutations. This study focused on the use of NGS for systematic prospective genetic profiling of patients with advanced NSCLC, both on solid and liquid biopsies.

Study Methodology

The analysis carried out at the Istituto Oncologico Veneto in Padua, Italy, included data from 235 patients with advanced NSCLC who did not have standard-detected mutations in EGFR/ALK/ROS1. Plasma or tumor tissue samples from these patients underwent gene panel sequencing using NGS. For plasma sample testing, the commercially available Guardant360 kit, covering 73 genes, was used. Tissue samples were tested with the Oncomine Focus Assay, covering 59 genes.

Results

Plasma sample testing was performed on 209 patients, of which 78 (37.3%) also had tumor tissue samples tested in parallel. In 26 patients, only tumor tissue was tested. Half of the tumor tissue samples were deemed unevaluable, and in a total of 13 out of 52 evaluable samples (25%), a mutation targetable with therapy was found. Such a mutation was also found in 31 (14.8%) plasma samples.

Patients who received targeted therapy had a longer median overall survival (OS) compared to others (median OS not reached vs. 9.1 months for patients without targeted therapy, 95% confidence interval [CI] 4.6−13.6; p = 0.046).

Conclusion

The systematic use of NGS in real clinical practice demonstrated the limitations of tumor tissue sample testing in patients with advanced NSCLC. It also showed that routine plasma sample testing could reveal mutations not detected by standard techniques, thereby expanding the range of patients who could benefit from targeted cancer therapy.

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Source: Bonanno L., Pavan A., Ferro A. et al. Clinical impact of plasma and tissue next-generation sequencing in advanced non-small cell lung cancer: a real-world experience. Oncologist 2020 Jun 18, doi: 10.1634/theoncologist.2020-0148 [Epub ahead of print].



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Clinical oncology Pneumology and ftiseology Laboratory
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