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Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
[THE IMPACT OF MOLECULAR PROFILING USING NEXT-GENERATION SEQUENCING IN ADVANCED LUNG CANCER]
Anna Belilovski Rozenblum1, Maya Ilouze2, Elizabeth Dudnik2
1Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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.
Insights
Next-Generation Sequencing (NGS) identifies targetable mutations in most lung cancer patients, enabling personalized treatment. This molecular testing is crucial for guiding therapy and improving outcomes in advanced lung cancer.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Advances in understanding lung cancer pathways have led to targeted therapies.
- Many lung adenocarcinomas harbor treatable driver mutations (e.g., RET, ERBB2, ROS1, ALK, EGFR).
- Next-Generation Sequencing (NGS) offers comprehensive genomic profiling beyond standard diagnostic tests.
Purpose of the Study:
- To assess the real-world impact of NGS-based tumor profiling on treatment decisions for advanced lung cancer patients.
- To determine the utility of NGS in identifying actionable genomic alterations.
- To evaluate the clinical benefit of NGS-guided therapy.
Main Methods:
- Retrospective analysis of 50 advanced lung cancer patients treated at Davidoff Cancer Center.
- Performance of broad, hybrid capture-based NGS genomic profiling.
- Review of patient charts for treatment decisions and outcomes.
Main Results:
- 84.8% of patients had at least one driver alteration identified by NGS.
- 45.7% of patients received targeted therapy based on NGS findings.
- NGS uniquely identified actionable mutations in 37.5% of treated patients, including 10 cases initially negative by standard testing.
Conclusions:
- NGS effectively identifies targetable genomic alterations in the majority of lung tumors.
- Implementing NGS for therapeutic decision-making is essential, potentially benefiting about half of patients with customized treatments.
- Multiplex testing via NGS is important for advanced lung cancer diagnosis.
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