Abstract
BackgroundThis study aims to clarify the prognostic role of epidermal growth factor receptor (EGFR) mutations in plasma of non-small cell lung cancer (NSCLC) for resistance to tyrosine kinase inhibitor (TKI), in correlation with clinical characteristics. A total of 94 Adenocarcinoma, clinical stage IV NSCLC patients with either E19del or L858R mutation were admitted to the prospective study from Jan-2016 to Jul-2018. EGFR mutations in plasma were detected by scorpions ARMS method. The Kaplan–Meier and Cox regression methods were used to estimate and test the difference of progression-free survival (PFS) and overall survival (OS) between groups. The prognostic power of each factor was appraised by the Bayesian Model Averaging (BMA) method.ResultsAmong 94 patients, 28 cases still are good responses according to the RECIST criteria and negative for EGFR mutations in plasma. Of 66 resistant patients, EGFR mutations were positive in plasma of 57 cases (86.4%) which was higher than the value of pre-treatment (48.5%). Of which, 17 patients (25.8%) have the occurrence of EGFR mutations in plasma earlier than progression 2.1 (0.6–7.9) months. The secondary T790M mutation was found in the plasma of 32 cases (48.5%). Median PFS and OS for the study subjects were 12.9 (11.0–14.2) and 29.5 (25.2–41.3) months, respectively. The post-treatment EGFR plasma test with brain and new metastasis were detected as independent prognostic factors for worse PFS (P = 0.008, 0.016 and 0.028, respectively). While EGFR plasma (P = 0.044) with bone metastasis at baseline (P = 0.012), new metastasis (P = 0.003), and high cfDNA concentration (P = 0.004) serve as the worse survival factors, surgery treatment helps to prolong OS in NSCLC treated with EGFR TKI (P = 0.012). BMA analysis identified EGFR plasma test as the strongest prognostic factor for both PFS and OS (possibility of 100% and 99.7%, respectively).ConclusionsEGFR plasma test is the powerfully prognostic factor for early resistance with EGFR TKI and worse survival in NSCLC regardless of clinical characteristics.
Highlights
This study aims to clarify the prognostic role of epidermal growth factor receptor (EGFR) mutations in plasma of non-small cell lung cancer (NSCLC) for resistance to tyrosine kinase inhibitor (TKI), in correlation with clinical characteristics
Treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) such as Erlotinib or Gefitinib helps to prolong the progression-free survival (PFS) time, increase the response rate, and minimize the side effects compared to standard chemotherapy treatment for non-small cell lung cancer (NSCLC) patients who carried the activating EGFR mutations [1, 2]
Patients and treatment evaluation A total of 94 Adenocarcinoma, stage IV NSCLC patients with either E19del or L858R mutation who were treated with Erlotinib or Gefitinib were selected for this study from January 2016 to July 2018 at Cho Ray hospital
Summary
This study aims to clarify the prognostic role of epidermal growth factor receptor (EGFR) mutations in plasma of non-small cell lung cancer (NSCLC) for resistance to tyrosine kinase inhibitor (TKI), in correlation with clinical characteristics. Treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) such as Erlotinib or Gefitinib helps to prolong the progression-free survival (PFS) time, increase the response rate, and minimize the side effects compared to standard chemotherapy treatment for non-small cell lung cancer (NSCLC) patients who carried the activating EGFR mutations (deletions in exon 19—E19del, and L858R substitution mutation in exon 21) [1, 2]. Intensive studies in the last decade have shown that various reasons were associated with acquired resistance to the first- and second-generation TKI, in which the secondary Threonine-790-Methionine substitution mutation (T790M) in exon 20 of the EGFR gene is the most common cause of TKI resistance (50–60%) [3] Patients with this acquired mutation will be switched to the treatment with third-generation TKI such as Osimertinib which now is a standard therapy with higher efficiency compared to Erlotinib or Gefitinib, and chemotherapy [4, 5]. The cell-free DNA (cfDNA) in plasma may serve as the surrogate sample with advantages of less invasion, fasting method, and convenient uses
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