Benefit of Targeted DNA Sequencing in Advanced Non-Small-Cell Lung Cancer Patients Without EGFR and ALK Alterations on Conventional Tests.

Background: Genetic sequencing testing has become widely used to inform treatment decisions for advanced non-small-cell lung cancer (NSCLC) patients. We analyzed benefits of genetic sequencing testing in real practice.

Patients And Methods: We retrospectively reviewed 209 NSCLC patients who had no EGFR and ALK alterations on routine molecular tests and underwent next-generation targeted DNA sequencing of 380 cancer-related genes between November 2013 and October 2016. Median patient age was 59 years. A total of 96 patients (46%) were never smokers, and 195 patients (93%) had adenocarcinoma.

Results: Among 209 total patients, 64 (31%) demonstrated actionable genetic alterations; 20 had EGFR mutations (6 L858R, 8 exon 19 deletions, 1 L861Q, 1 G719S, 4 exon 20 duplications), 4 ALK fusions, 9 ROS1 fusions, 6 BRAF V600E mutations, 15 RET fusions, 1 MET high-level amplification, 6 MET exon 14 skipping mutations, and 3 ERBB2 exon 20 insertion mutations. Of the 64 patients harboring actionable alterations, 28 patients received therapy targeted to their own actionable alterations (15 EGFR, 3 ALK, 1 ROS1, 8 RET, 1 BRAF). There were significant differences in overall survival between individuals with no actionable alterations, those with actionable alterations but no targeted therapy, and those with actionable alterations and targeted therapy (20.1 vs. 17.1 vs. 66.2 months, P < .001).

Conclusion: The results of targeted DNA sequencing testing could provide improved treatment options for some NSCLC patients and result in a survival benefit to NSCLC patients with no EGFR and ALK alterations on routine tests who are treated with targeted therapy.