Correlation between progression‐free survival, tumor burden, and circulating tumor DNA in the initial diagnosis of advanced‐stage EGFR‐mutated non‐small cell lung cancer

• Published in: Thoracic cancer 2018-09, Vol.9 (9), p.1104-1110
• Main Authors: Lee, Yunkyoung, Park, Sojung, Kim, Woo Sung, Lee, Jae Cheol, Jang, Se Jin, Choi, Jene, Choi, Chang‐Min
• Format: Article
• Language: English
• Subjects: Aged; Analysis; Biomarkers, Tumor; Biopsy; Cancer; Carcinoma, Non-Small-Cell Lung - diagnosis; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - mortality; Care and treatment; Circulating Tumor DNA; Clinical outcomes; Deoxyribonucleic acid; Development and progression; Diagnosis; Disease; DNA; EGFR‐tyrosine kinase inhibitor (TKI); ErbB Receptors - genetics; Female; Genetic aspects; Genetic research; Humans; Kaplan-Meier Estimate; Laboratories; Lung cancer; Lung cancer, Non-small cell; Lung Neoplasms - diagnosis; Lung Neoplasms - genetics; Lung Neoplasms - mortality; Male; Metastasis; Methods; Middle Aged; Mutation; Neoplasm Staging; non‐small cell lung cancer; Odds Ratio; Original; Patients; Prognosis; progression‐free survival; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Quantitative analysis; sensitivity; Studies; Tumor Burden; Tyrosine
• ISSN: 1759-7706; 1759-7714
• DOI: 10.1111/1759-7714.12793

Background This study was conducted to identify whether the presence of circulating tumor DNA (ctDNA) in plasma before treatment with EGFR‐tyrosine kinase inhibitors (TKIs) is associated with clinical outcomes. Methods Fifty‐seven pairs of tissues and plasma samples were obtained from patients with NSCLC adenocarcinoma harboring activating EGFR mutations before the administration of EGFR‐TKI treatment. ctDNA mutation was identified using the PANAMutyper EGFR mutation kit. Both qualitative and quantitative analyzes of the data were performed. Results Concordance rates with tissue biopsy were 40.4% and 59.6% for the qualitative and quantitative methods, respectively. Bone metastasis showed a statistically significant correlation with ctDNA detection (odds ratio 3.985, 95% confidence interval [CI] 1.027–15.457; P = 0.046). Progression‐free survival (PFS) was significantly shorter in the group detected with ctDNA than in the undetected ctDNA group (median PFS 9.8 vs. 20.7 months; hazard ratio [HR] 2.30, 95% CI 1.202–4.385; P = 0.012). Detection of ctDNA before treatment with EGFR‐TKIs (HR 2.388, 95% CI 1.138–5.014; P = 0.021) and extra‐thoracic lymph node metastasis (HR 13.533, 95% CI 2.474–68.747; P = 0.002) were independently associated with PFS. Six of 11 patients (45.5%) monitored by serial sampling showed a dynamic change in ctDNA prior to disease progression. Conclusion Quantitative testing can increase the sensitivity of the ctDNA detection test. Patients with detectable ctDNA had significantly shorter PFS after receiving EGFR‐TKIs than those with undetectable ctDNA. Tumor burden may be associated with plasma ctDNA detection. A shorter PFS was associated with detection of ctDNA and extra‐thoracic lymph node metastasis. Dynamic changes in the ctDNA level may help predict clinical outcomes.