Is genetic testing for lung cancer recommended?

From the Guidelines

Genetic testing for lung cancer is recommended for patients with advanced lung adenocarcinoma, irrespective of clinical characteristics, to identify targetable molecular alterations such as EGFR, ALK, and ROS1 mutations. This recommendation is based on the updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors, as outlined in the study by the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology 1.

The guideline suggests that ROS1 testing should be performed on all patients with advanced lung adenocarcinoma, and that ROS1 IHC may be used as a screening test, but positive results should be confirmed by a molecular or cytogenetic method. Additionally, the guideline recommends that BRAF, RET, ERBB2 (HER2), KRAS, and MET testing may be included in larger testing panels, particularly when routine EGFR, ALK, and ROS1 testing are negative 1, 2, 3.

Next-generation sequencing (NGS) methods are preferred over multiple single-gene tests to identify other treatment options beyond EGFR, ALK, and ROS1, as they enable the simultaneous assessment of multiple genes and can detect fusions/rearrangements and copy number changes 4. The choice between amplicon-based and hybrid capture-based NGS assays depends on the specific clinical scenario, with amplicon sequencing being more suitable for simpler assays and capture-based methods being more suitable for larger sets of genes or genomic regions.

Key considerations for genetic testing in lung cancer include:

• The type of lung cancer, with adenocarcinoma being the most common type to harbor targetable molecular alterations
• The clinical characteristics of the patient, such as age and smoking history
• The availability of tissue for testing, with cytology samples being acceptable in some cases
• The potential benefits and limitations of different testing methods, including NGS and single-gene assays.

Overall, genetic testing for lung cancer should be guided by the latest clinical practice guidelines and should take into account the individual patient's clinical characteristics and the availability of effective targeted therapies.

From the FDA Drug Label

Select patients for first-line treatment of metastatic NSCLC with GILOTRIF based on the presence of non-resistant EGFR mutations in tumor specimens [see Clinical Pharmacology (12.1), Clinical Studies (14. 1)]. Information on FDA-approved tests for the detection of EGFR mutations in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics.

Genetic testing for lung cancer is recommended to select patients for first-line treatment of metastatic NSCLC with certain medications, such as GILOTRIF, based on the presence of non-resistant EGFR mutations in tumor specimens 5.

From the Research

Genetic Testing for Lung Cancer

• Genetic testing for lung cancer is a topic of ongoing research, with several studies investigating its role in identifying high-risk individuals and informing treatment decisions 6, 7, 8, 9, 10.
• A study published in 2021 discussed the use of risk prediction models (RPMs) to identify high-risk individuals for lung cancer screening, highlighting the potential for genetic risk factors to improve the accuracy of these models 6.
• Another study from 2020 reviewed the current status and future prospects of cancer genomics in lung cancer, including the use of genomic analysis to identify targeted therapy options 7.
• A 2022 study examined the use of next-generation sequencing (NGS) in patients with advanced non-small cell lung cancer, finding that NGS testing may help avoid potentially missed targeted therapy options and improve testing uptake for recently approved biomarkers 8.
• The use of NGS for genetic testing of lung cancer specimens has been shown to be feasible and effective, with high concordance rates and low costs compared to conventional methods 9.
• A 2013 review discussed the use of genetic markers in nonsmall cell lung cancer, highlighting the importance of testing for driver mutations such as EGFR and ALK, which can inform treatment decisions and improve outcomes 10.

Recommendations for Genetic Testing

• The 2018 United States and international lung cancer and pathology guidelines recommend testing for EGFR, ALK, ROS1, and BRAF genes in patients with advanced non-small cell lung cancer 8.
• Genetic testing for driver mutations is useful in identifying patients with nonsmall cell lung cancer who are likely to respond to targeted therapy, particularly those with adenocarcinoma and advanced-stage cancer 10.
• NGS testing may be a suitable strategy for lung cancer, allowing for the simultaneous testing of multiple genetic markers and informing treatment decisions 9.