Canadian Study Explores Use of Liquid Biopsies in Advanced NSCLC

Next-generation sequencing (NGS) of cell-free DNA (cfDNA) may improve diagnostic testing in advanced lung cancer.

Next-generation sequencing (NGS) of cell-free DNA (cfDNA) obtained from blood samples may improve diagnostic testing in patients with advanced non-small cell lung cancer (NSCLC).

The research was published as part of the IASLC 2020 Lung Cancer Hot Topic: Liquid Biopsy Virtual Conference. A liquid biopsy uses a blood sample to uncover genetic information about a tumor and can be used where standard tissue biopsies are not feasible, such as tumor location.

The study, involving 210 patients in 2 cohorts, took place at 6 Canadian hospitals.

Cohort 1 included 150 treatment-naïve patients with measurable disease and smoking history of fewer than 10 packs of cigarettes per year. Cohort 2 enrolled 60 patients with known oncogenic drivers whose disease progressed on tyrosine kinase inhibitors (TKIs).

After excluding variants of unknown significance and synonymous alterations, 118 patients in cohort 1 (79%) had more than 1 alteration detected by G360 test (304 alterations detected in 35 genes). Of these, 284 alterations were considered actionable with FDA-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 nonV600E (1.1%).

In cohort 2, 53 patients (85%) had more than 1 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 non-driver mutations.

Twenty-seven patients (14.0% in cohort 1; 10% in cohort 2) had no alterations detected by G360. In samples with alterations detected, the median number of alterations per patient was 3 (range 1-17). The median time to reporting of G360 was 7 days (range 5-27).

The idea of using blood biopsies first is growing as it may be faster, less expensive, and more specific compared with standard tissue profiling.

"Over 80% of patients with advanced NSCLC had characterized genomic alterations detected in cfDNA. At least 56% of treatment-naïve patients and 37% of TKI-resistant patients had clinically actionable alterations detected," said study lead by Natasha Leighl, MD, Princess Margaret Cancer Centre, Toronto, Canada, in a statement.

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