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Gregory J. Riely, MD, PhD


Use of Liquid Biopsy in Detecting Resistance After Targeted Therapy in Advanced NSCLC

By: Emily Rhode
Posted: Thursday, May 25, 2023

A study assessing the efficacy of liquid biopsy in detecting resistance after targeted therapy as well as circulating-tumor DNA (ctDNA) in patients with advanced non–small cell lung cancer (NSCLC) and ALK, ROS1, or RET fusions found that the noninvasive technique was able to detect resistance mechanisms in just one-third of patients and was often unsuccessful in the detection of ctDNA. These results were presented by Mihaela Aldea, MD, PhD, of Institut de Cancérologie Gustave Roussy, Villejuif, France, and colleagues at the American Association for Cancer Research (AACR) Annual Meeting 2023 (Abstract 1034/11).

The study was conducted between December 2020 and June 2022, when 597 patients with advanced NSCLC at a single institution had at least one liquid biopsy assessed. Plasma was collected from treatment-naive patients and/or at the time of disease progression. The biopsy assessment included a panel of 324 genes. Clinical and molecular data were recorded from patients with known ALK, ROS1, or RET fusions. Of them, 68 patients who had a total of 83 liquid biopsies were included in the efficacy evaluation, which classified liquid biopsies as positive if fusion or resistance mutations were detected and negative if no ctDNA was found.

In 55 of 83 total cases (66%), the liquid biopsy was positive, whereas positivity rates were 93% and 59% in treatment-naive and pretreated patients, respectively. Limited disease progression (P < .001) and active treatment at the time of liquid biopsy (P < .05) were both significantly associated with a negative liquid biopsy. Liquid biopsies were performed at disease progression after targeted therapies a total of 47 times; of them, 15% found on-target resistance, 21% found bypass resistance, 21% had no explainable resistance, and 43% were negative. Several bypass resistance genetic alterations were found in the analysis.

Disclosure: Disclosures for the study authors can be found at

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