Characterization of Liver Metastasis and Its Effect on Targeted Therapy in EGFR-mutant NSCLC: A Multicenter Study

The risk factors for liver metastasis (LM) in patients with non-small-cell lung cancer (NSCLC) and its impact on the effect of first-line epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) remains controversial. Our data suggest that EGFR mutation is not an independent risk factor for LM in NSCLC patients. However, LM is the negative predictive factor for first-line EGFR-TKI therapy for patients with EGFR-mutant NSCLC. Background: The risk factors for liver metastasis (LM) in patients with nonesmall-cell lung cancer (NSCLC) remain unknown. Whether LM predicts for the effect of first-line epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in patients with EGFR-mutant NSCLC needs to be explored. Patients and Methods: A total of 598 NSCLC patients from 3 centers underwent EGFR testing, and 293 had EGFR-mutant NSCLC. Of the 598 NSCLC patients, 99 had LM; 56 patients with EGFR-mutant NSCLC received EGFR-TKIs as first-line therapy. Results: EGFR mutation was not associated with LM in NSCLC patients (relative ratio, 1.305, P = .261). In the EGFR-mutant group that received first-line EGFR-TKIs, patients with LM had shorter progression-free survival (PFS; 7.5 vs. 11.8 months; P = .0003) and overall survival (OS; 20.8 vs. 30.6 months; P = .0190) than patients without LM. The significant difference in PFS was observed in both patients with EGFR exon 19 deletion (19del) and Leu858Arg mutation (L858R). However, patients with EGFR 19del and LM showed marginally significantly shorter OS (P = .0531) and patients with EGFR L858R and LM had OS similar to that of patients without LM (P = .1883). Regardless of EGFR status, patients with LM who received first-line chemotherapy had PFS and OS similar to those of patients without LM. Univariate analyses identified only never smoking (hazard ratio, 0.536; P = .012) was significantly associated with better OS for patients with NSCLC and LM. Conclusion: EGFR mutation is not an independent risk factor for LM in NSCLC patients. However, the presence of LM is a negative predictive factor for first-line EGFR-TKI therapy for patients with EGFR-mutant NSCLC. (C) 2017 Elsevier Inc. All rights reserved.