Targeted DNA Sequencing Helps Find Targeted Therapy for Patients with NSCLC
Gene sequencing has become a key tool in deciding the treatment for patients with non-small cell lung cancer (NSCLC). At a university in Seoul, South Korea, a retrospective analysis of the benefits of targeted genetic testing in real clinical practice was conducted.
Genomic Changes and Targeted Therapy for NSCLC
Advances in studying genomic changes in NSCLC have completely changed the concept of treating this disease. Targeted therapies using epidermal growth factor receptor (EGFR) inhibitors, tyrosine kinase inhibitors (TKI), and anaplastic lymphoma kinase (ALK) inhibitors have become the standard treatment for patients with genetic changes suitable for targeted therapy, replacing chemotherapy. Mutations in the EGFR and ALK genes are now routinely tested before initiating NSCLC treatment.
The development of next-generation sequencing (NGS) techniques has provided a highly effective approach to identifying multiple genomic changes. The sensitivity of NGS in detecting somatic mutations in cancer is higher compared to traditional molecular testing, allowing the detection of changes that routine testing may miss. However, there is currently no evidence that the use of NGS actually improves treatment outcomes in NSCLC patients. Moreover, the high cost of whole-genome sequencing must be taken into account.
The authors of the presented study thus decided to conduct a retrospective analysis of a cohort of patients who underwent targeted sequencing of a panel of genes associated with cancer in routine clinical practice.
Study Methodology
The analysis included data from 209 NSCLC patients, in whom routine molecular testing did not reveal any changes in the EGFR or ALK genes and who subsequently underwent DNA sequencing using the NGS technique. A panel of 380 cancer-related genes was sequenced.
The median age of the patients was 59 years, with 46% having never smoked. 93.3% had adenocarcinoma, 2.9% had pleomorphic carcinoma, 1.9% had squamous cell carcinoma, 0.5% had sarcomatoid carcinoma, and 1.4% had poorly differentiated tumors.
Results
DNA sequencing revealed genomic changes suitable for targeted therapy in 31% of patients. These included mutations in the EGFR, BRAF, MET, or ERBB2 genes, as well as ALK, ROS1, or RET fusions. Out of the 64 patients with actionable changes, 28 received appropriate targeted therapy (15 cases of anti-EGFR, 3 of anti-ALK, 1 of anti-ROS, 8 of anti-RET, and 1 of anti-BRAF therapy).
Significant differences were observed in overall survival (OS) among patients without actionable changes (OS 20.1 months), patients with actionable changes who did not receive targeted therapy (OS 17.1 months), and patients who received targeted therapy (OS 66.2 months; p < 0.001).
Conclusion
Targeted DNA sequencing may offer better treatment options for some NSCLC patients. Patients with negative routine tests for EGFR and ALK mutations may still significantly benefit from targeted therapy based on the sequencing of a broader panel of genes.
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Source: Byeon S., Lee B., Park W.-Y. et al. Benefit of targeted DNA sequencing in advanced non-small-cell lung cancer patients without EGFR and ALK alterations on conventional tests. Clin Lung Cancer 2020; 21 (3): e182–e190, doi: 10.1016/j.cllc.2019.11.006.
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