EGFR Mutation Status in Lung Adenocarcinoma-Associated Malignant Pleural Effusion and Efficacy of EGFR Tyrosine Kinase Inhibitors
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Purpose Malignant pleural effusions (MPEs) are often observed in lung cancer, particularly adenocarcinoma. The aim of this study was to investigate epidermal growth factor receptor (EGFR) mutation status in lung adenocarcinoma-associated MPEs (LA-MPEs) and its correlation with efficacy of EGFR tyrosine kinase inhibitor (TKI) therapy. Materials and Methods Samples comprised 40 cell blocks of pathologically-confirmed LA-MPEs collected before the start of EGFR TKI therapy. EGFR mutation status was re-evaluated by peptide nucleic acid clamping and the clinical outcomes of EGFR TKItreated patients were analyzed retrospectively. Results EGFR mutations were detected in 72.5% of LA-MPE cell blocks (29/40). The median progression- free survival for patients with EGFRmutations in LA-MPEs was better than that for patients with wild-type EGFR (7.33 months vs. 2.07 months; hazard ratio, 0.486; 95% confidence interval, 0.206 to 1.144; p=0.032). The objective response rate (ORR) of 26 patients with EGFR mutations in LA-MPEs among the 36 patients with measurable lesions was 80.8%, while the ORR of the 10 patients with wild-type EGFR in LA-MPEs was 10% (p < 0.001). Among the 26 patients with EGFR mutations in LA-MPEs, the ORR of target lesions and LA-MPEs were 88.5% and 61.5%, respectively (p=0.026). Conclusion EGFRmutation status in cell blocks of LA-MPEs confirmed by pathologic diagnosis is highly predictive of EGFR TKI efficacy. For patients with EGFRmutations in LA-MPEs, the response to EGFR TKIs seems to be worse for pleural effusions than for solid tumors.
Abstract
Purpose Malignant pleural effusions (MPEs) are often observed in lung cancer, particularly adenocarcinoma. The aim of this study was to investigate epidermal growth factor receptor (EGFR) mutation status in lung adenocarcinoma-associated MPEs (LA-MPEs) and its correlation with efficacy of EGFR tyrosine kinase inhibitor (TKI) therapy. Materials and Methods Samples comprised 40 cell blocks of pathologically-confirmed LA-MPEs collected before the start of EGFR TKI therapy. EGFR mutation status was re-evaluated by peptide nucleic acid clamping and the clinical outcomes of EGFR TKItreated patients were analyzed retrospectively. Results EGFR mutations were detected in 72.5% of LA-MPE cell blocks (29/40). The median progression- free survival for patients with EGFRmutations in LA-MPEs was better than that for patients with wild-type EGFR (7.33 months vs. 2.07 months; hazard ratio, 0.486; 95% confidence interval, 0.206 to 1.144; p=0.032). The objective response rate (ORR) of 26 patients with EGFR mutations in LA-MPEs among the 36 patients with measurable lesions was 80.8%, while the ORR of the 10 patients with wild-type EGFR in LA-MPEs was 10% (p < 0.001). Among the 26 patients with EGFR mutations in LA-MPEs, the ORR of target lesions and LA-MPEs were 88.5% and 61.5%, respectively (p=0.026). Conclusion EGFRmutation status in cell blocks of LA-MPEs confirmed by pathologic diagnosis is highly predictive of EGFR TKI efficacy. For patients with EGFRmutations in LA-MPEs, the response to EGFR TKIs seems to be worse for pleural effusions than for solid tumors.
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