Lack of CGP Testing May Result in Missed Therapy Options in NSCLC

Comprehensive genomic profiling (CGP) testing needs to be utilized more in advanced non–small cell lung cancer (aNSCLC) because testing for EGFR, ALK, ROS1, and BRAF genes could help patients avoid potentially missed targeted therapy options, resulting in better clinical outcomes.

The results from a real-world analysis, published in Lung Cancer, support greater utilization of guideline-recommended broad-panel next-generation sequencing (NGS) in clinical practice.

Guidelines from the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology establish minimum requirements for testing of EGFR, ALK, ROS1, and BRAF genes because they have FDA-approved targeted therapy options in patients with newly diagnosed nonsquamous aNSCLC.

Although NGS is listed in several guidelines, little is known about the patterns of use and clinical features of NGS and other non–NGS-based CGP testing in real-world settings. The authors examined use of CGP testing among patients with newly diagnosed aNSCLC who have received care in the US community oncology setting.

The researchers analyzed the Flatiron Health electronic health record–derived database, which has information on over 2.4 million US patients with cancer from about 800 care sites. For inclusion, patients had to have received a diagnosis of nonsquamous aNSCLC between January 1, 2018, and June 30, 2019, and had begun first-line therapy within 90 days of their diagnosis. The patients were grouped based on the type of biomarker test they received between 30 days prior to receiving a diagnosis for advanced disease and the start of first-line therapy.

In total, 3050 patients were included in the analysis, of whom 2356 received any type of genomic testing. Among those who received testing, 1406 (59.7%) received NGS testing. Unsuccessful genotyping was found in 13.2% of the patients who received NGS testing and 52.2% of patients who received non-NGS CGP testing.

The mean (SD) age of the patients was 68.3 (9.9) years, 50.2% (n = 1532) were male, and 66.0% (n = 2012) were White. By disease state, 4.7% had stage I, 2.4% had stage II, 13.0% had stage III, 1.0% had stage IIIc, and 78.3% had stage IV. Also, 84.9% of the cohort had a history of smoking.

Among the patients who were tested with NGS, 10.0% had a potentially missed targeted therapy option, significantly lower than the patients who were tested with non-NGS CGP (40.2%). For the patients who were tested using a non-NGS test, a potential targeted therapy was found in 20.7% of cases and a potentially missed targeted therapy option was detected in 40.2%.

Although all 4 genes recommended by guidelines for testing were evaluated in over 92.0% of patients who were tested with NGS, when only non-NGS testing was used, BRAF and ROS1 were examined less often than EGFR and ALK.

“Our results support an increasing clinical need for broader NGS-based testing, which tends to be more cost- and time-effective than single-gene testing, in patients with aNSCLC. This supports the application of standardized testing algorithms in pathology to ameliorate waiting for individual test results (ie, EGFR, BRAF, ALK, ROS1), and any other approved genomic biomarker should be tested by pathologists in every patient with stage IV nonsquamous NSCLC by default,” the authors wrote.

The main limitations of this study were that reasons why patients received genomic testing were unavailable and some patients could have tested positive for rare alterations to genes that were not documented in the data. However, the authors said that the frequency at which these rare alterations are detected is so infrequent that they likely would not have had a major impact on the study results.

Reference

Paz-Ares L, Gondos A, Saldana D, et al. Genomic testing among patients with newly diagnosed advanced non-small cell lung cancer in the United States: a contemporary clinical practice patterns study. Lung Cancer. 2022;167(2022):41-48. doi:10.1016/j.lungcan.2022.01.021