518P - Real world prospective clinical impact of finding actionable genomic alterations by plasma cell-free DNA next generation sequencing in advanced non-small cell lung cancer

Background

Next-generation sequencing (NGS) of cell-free circulating tumor DNA (cfDNA) enables noninvasive simultaneous genomic analysis. Although detecting genomic alterations in plasma has been shown to be reliable and reproducible, real-world data and its clinical impact are yet limited.

Methods

We prospectively analyzed 147 advanced NSCLC patients between December 2018 and July 2019. We collected information regarding baseline characteristics including age, gender, mutation status, date of each biopsy, and response of treatment. Addition to conventional tissue analysis, we used cfDNA NGS (Guardant360; Guardant Health, Inc., Redwood City, California) to identify targetable genomic alterations in plasma. Variants were considered actionable if they were part of the Onco-KB precision oncology knowledge database and classified in four levels of actionability based on their preclinical or clinical evidence.

Results

Among 147 patients, 143 (97.3%) patients had detectable levels of cfDNA at plasma. The patient with adenocarcinoma and squamous cell carcinoma were 116 (81.1%) and 20 (14.0%) respectively. Forty patients (28.0%) were treatment-naïve and one hundred three patients (72.0%) were with progressive disease after chemotherapy or immunotherapy. Potentially actionable level 1-4 genomic alterations were detected in 48 cases (33.5%), of which 15 patients (10.5%) had level 1-2 alterations. Six patients changed treatment regimen according to the result of cfDNA NGS. At the time of data cut-off, all the responses of treatment-changed patients (n = 6) were stable disease with ongoing treatment.

Conclusions

Real world cfDNA testing identified actionable genomic alterations in NSCLC which were not identified in conventional tissue biopsy with high feasibility. This prospective study demonstrated that profiling of NSCLC using cfDNA NGS testing can be more efficient strategy for deciding the therapeutic options at initial diagnosis and after progression.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.