Background: In the last decade, important advances in understanding the lung cancer cellular signal pathways have led to the designing of targeted drugs that significantly prolong survival. Recent data shows that 64% of lung adenocarcinomas harbor at least one activating driver mutation, including treatable mutations such as RET, ERBB2 (HER-2) and ROS1 gene mutations, besides the regularly screened ALK and EGFR genes. Next-Generation Sequencing (NGS) reveals more clinically meaningful genomic alterations as compared to currently used diagnostic tests. However, the clinical impact of NGS testing merits further investigation.
Objectives: To evaluate the impact of NGS-based tumor profiling on therapeutic decision making in the real life setting in advanced lung cancer patients.
Methods: The study population included 50 lung cancer patients who were treated at Davidoff Cancer Center, Rabin Medical Center in 2011-2015, and for whom a broad, hybrid capture-based NGS genomic profiling test was performed. The data was retrospectively collected from patient charts.
Results: 39 of 46 included patients (84.8%) had one or more driver alternations, and a targeted agent was administered according to alteration discovered in 21 of 46 cases (45.7%). 15 (37.5%) treated patients were exclusively detected by NGS. The most frequent drivers were EGFR (26.1%), KRAS (19.6%), ALK (13%), STK11 (10.9%) and RET (8.7%). Interestingly, 10 patients became EGFR and ALK positive by NGS after the previous standard local molecular testing was negative.
Conclusions: Molecular testing using NGS can reveal a targetable genomic alteration in the vast majority of lung tumors. Its broad use for therapeutic decision making is essential since approximately half of the patients can benefit from customized treatment upon testing results.
Discussion: Although this topic needs to be further assessed in large randomized controlled trials, our positive results emphasize the importance of multiplex testing as a diagnostic test in advanced lung cancer patients. The implementation of NGS at Rabin Medical Center in the near future is highly anticipated.