Next-generation sequencing of cell-free DNA (cfDNA) obtained from blood samples may improve diagnostic testing in patients with advanced non–small cell lung cancer (NSCLC) and may also be faster and less expensive than standard tissue profiling, according to research presented by Natasha B. Leighl, MD, MMSc, FRCPC, FASCO, and colleagues at the International Association for the Study of Lung Cancer (IASLC) 2020 Lung Cancer Hot Topic: Liquid Biopsy Virtual Conference (Abstract VP01.22).
Researchers led by Dr. Leighl, of the Princess Margaret Cancer Centre in Toronto, examined the clinical utility and treatment outcomes with liquid biopsy in patients with advanced NSCLC from the perspective of the Canadian public health-care system.
Natasha B. Leighl, MD, MMSc, FRCPC, FASCO
Dr. Leighl and her colleagues at six Canadian hospitals organized 210 patients into two cohorts. Cohort 1 included 150 treatment-naive patients with measurable disease and a smoking history of fewer than 10 packs of cigarettes per year. Cohort 2 enrolled 60 patients with known oncogenic drivers whose disease progressed during treatment with tyrosine kinase inhibitors.
After excluding variants of unknown significance and synonymous alterations, 118 patients in cohort 1 (79%) had more than one alteration detected by G360 test (304 alterations detected in 35 genes). Of these, 284 alterations were considered actionable with U.S. Food and Drug Administration–approved drugs or available clinical trials. Actionable targets included EGFR (32.0%), ERBB2 (3.2%), MET (3.2%), ALK (1.4%), KRAS G12C (1.1%), and ROS1 (0.4%). Additional clinically relevant alterations included TP53 (27.8%), KRAS non-G12C (3.9%), PIK3CA (3.9%), and BRAF non-V600E (1.1%).
In cohort 2, 53 patients (85%) had more than one characterized genomic alteration detected, with a total of 165 alterations in 28 genes, including EGFR (45.8%, 5 were C797S), ALK (fusions, 3.3%; mutations, 2.0%), BRAF (V600E, 0.7%; other, 3.3%), MET (amplification, 2.0%; exon 14, 0.7%), FGFR3 (0.7%), and RET (0.7%), as well as nondriver mutations. Twenty-seven patients (14.0% in cohort 1 and 10% in cohort 2) had no alterations detected by G360. In samples with alterations detected, the median number of alterations per patient was three (range = 1–17). The median time to reporting of G360 was 7 days (range = 5–27).
“Over 80% of patients with advanced NSCLC had characterized genomic alterations detected in cfDNA. At least 56% of treatment-naive patients and 37% of patients [resistant to treatment with tyrosine kinase inhibitors] had clinically actionable alterations detected,” said Dr. Leighl. Liquid biopsy is an important and timely method of molecular diagnosis in newly diagnosed patients with advanced NSCLC and in the setting of targeted therapy resistance.