Impact of detecting plasma EGFR mutations with ultrasensitive liquid biopsy in outcomes of NSCLC patients treated with first- or second-generation EGFR-TKIs

• Published in: Cancer biomarkers : section A of Disease markers Vol. 32; no. 2; pp. 123 - 135
• Main Authors: Arrieta, Oscar, Hernandez-Martinez, Juan-Manuel, Montes-Servín, Edgar, Heredia, David, Cardona, Andrés F, Molina-Romero, Camilo, Lara-Mejía, Luis, Diaz-Garcia, Diego, Bahena-Gonzalez, Antonio, Mendoza-Oliva, Dolores L
• Format: Journal Article
• Language: English
• Published: Netherlands IOS Press BV 01.01.2021
• Subjects: Adult; Aged; Aged, 80 and over; Biopsy; Carcinoma, Non-Small-Cell Lung - blood; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - mortality; Clinical trials; Disease Progression; DNA Mutational Analysis; Epidermal growth factor; Epidermal growth factor receptors; ErbB Receptors - blood; ErbB Receptors - genetics; Female; Growth factors; Health services; Humans; Kinases; Liquid Biopsy; Lung cancer; Lung Neoplasms - blood; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - mortality; Male; Metastases; Metastasis; Middle Aged; Mutation; Non-small cell lung carcinoma; Patients; Plasma; Progression-Free Survival; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Protein-tyrosine kinase; Risk Assessment - methods; Risk Assessment - statistics & numerical data; Small cell lung carcinoma; Survival; Tumors; Tyrosine; EGFR-TKI resistance; clinical progression; ctDNA; liquid biopsy; lung adenocarcinoma
• ISSN: 1574-0153; 1875-8592
• DOI: 10.3233/CBM-203164

Few trials have evaluated the utility of liquid biopsies to detect epidermal growth factor receptor mutations (EGFRm) at the time of response evaluation and its association with the clinical characteristics and outcomes of non-small-cell lung cancer (NSCLC) patients. This study aimed to evaluate, in a real-world clinical setting, the prevalence of plasma EGFRm and its association with the clinical characteristics, response and survival outcomes of NSCLC patients under treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKIs). This observational study enrolled advanced or metastatic NSCLC patients, with confirmed tumor EGFRm, receiving treatment with first- or second-generation EGFR-TKIs. Blood samples for the detection of plasma EGFRm were collected at the time of response evaluation and processed using the Target Selector™ assay. The main outcomes were the detection rate of plasma EGFRm, median Progression-Free Survival (PFS) and Overall Survival (OS) according to plasma EGFR mutational status. Of 84 patients, 50 (59.5%) had an EGFRm detected in plasma. After a median follow-up of 21.1 months, 63 patients (75%) had disease progression. The detection rate of plasma EGFRm was significantly higher in patients with disease progression than in patients with partial response or stable disease (68.3% versus 33.3%; P< 0.01). PFS and OS were significantly longer in patients without plasma EGFRm than among patients with plasma EGFRm (14.3 months [95% CI, 9.25-19.39] vs 11.0 months [95% CI, 8.61-13.46]; P= 0.034) and (67.8 months [95% CI, 39.80-95.94] vs 32.0 months [95% CI, 17.12-46.93]; P= 0.006), respectively. A positive finding in LB was associated with the presence of ⩾ 3 more metastatic sites (P= 0.028), elevated serum carcinoembryonic (CEA) at disease progression (P= 0.015), and an increase in CEA with respect to baseline levels (P= 0.038). In NSCLC patients receiving EGFR-TKIs, the detection of plasma EGFRm at the time of tumor response evaluation is associated with poor clinical outcomes.