Plasma epidermal growth factor receptor mutation analysis and possible clinical applications in pulmonary adenocarcinoma patients treated with erlotinib

Abstract

Abstract. Tumor epidermal growth factor receptor (EGFR) mutation analysis is significant for making treatment decisions for metastatic pulmonary adenocarcinoma. However, less than half of patients have adequate tumor samples for mutation analysis. Patients with adenocarcinoma of the lungs who were due to receive erlotinib treatment were included in the present study. Tumor EGFR mutation status was analyzed using DNA sequencing. Plasma specimens from the patients were collected prior to erlotinib treatment. The plasma-free DNA EGFR mutation status was analyzed using the PCR clamp method. A total of 54 consecutive patients were included in the study. The plasma-free DNA EGFR mutation status of the 54 patients was analyzed. Only 30 patients had adequate tumor samples for EGFR analysis, including 15 with activating mutations (exon 19 deletions or L858R). EGFR-activating mutations were detected in the plasma-free DNA in 25 of 54 patients. The response rate was 86.7 and 33.3% in patients with and without tumor activating mutations, respectively (p=0.002). The response rate was 68 and 31% based on the patients' plasma-free DNA EGFR mutation status, respectively (p=0.013). No significant difference in progression-free survival (PFS) was observed between patients with and without EGFR-activating mutations, according to data from tumor tissue or plasma-free DNA analysis, although the median PFS time was longer for those patients with EGFR-activating mutations in plasma samples.Plasma EGFR mutation analysis is useful for adenocarcinoma patients who have no or inadequate tumor samples available for EGFR examination. Patients with plasma EGFR-activating mutations had an improved response rate and a statistically insignificant longer PFS.

Target therapy in NSCLC patients: Relevant clinical agents and tumour molecular characterisation

“…Subsequent studies have attempted to confirm these results in a larger case series (75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85)(86)(87)(88)(89). Using different methodologies, results of the majority of those studies identified identical serum/plasma, with tissue EGFR mutations being reported in >70% of patients (74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85)(86)(87)(88)(89) (Table I).…”

Blood as a Substitute for Tumor Tissue in Detecting EGFR Mutations for Guiding EGFR TKIs Treatment of Nonsmall Cell Lung Cancer

“…The participants in 12 included studies 14 – 18 , 20 , 31 – 33 , 35 , 41 , 42 were in stages III–IV and 6 studies 19 , 27 , 37 , 40 , 43 , 44 in I–IV. Thirteen studies 14 , 15 , 18 – 20 , 28 , 31 , 35 – 38 , 42 , 44 tested EGFR mutations in plasma and 12 studies 16 , 17 , 27 , 29 , 30 , 32 – 34 , 39 – 41 , 43 in serum. Direct sequencing and scorpion amplification refractory mutation system (SARMS) were the main methods used for mutation test, which were adopted in 8 16 – 19 , 28 , 30 , 39 , 40 and 7 18 , 29 , 34 – 36 , 38 , 41 studies, respectively.…”

“…Eight studies 14 , 16 – 19 , 28 , 30 , 38 , 41 with a total of 564 patients contributed to the meta-analysis of EGFR mutations (exons 19 and 21) and survival. The pooled HR for PFS was larger in blood (HR: 0.72; 95% CI 0.64–0.80) than in tumor tissue (HR: 0.57; 95% CI 0.39–0.85) (Figure 3 ).…”

Liquid Biopsy and NSCLC

“…Up to now, a lot of retrospective studies have indicated that detection of driver gene mutations in ctDNA of patients with NSCLC is feasible and reliable [63][64][65][66] and can represent a good predictor of clinical response with relevant implications for patient management. In particular for advanced NSCLCs, detection of EGFR L858R mutations in cfDNA can be performed using several platforms with a high sensitivity [67]. An additional recent study from Marchetti et al provides the first strong correlation between the EGFR copy number mutation detection in the first days of treatment and clinical response to TKI treatments with relevant implications for NSCLCs management [68].…”