Usefulness of Bronchoscopic Rebiopsy of Non-Small Cell Lung Cancer with Acquired Resistance to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor

Abstract

<b>Background</b>: Approximately 50% of non-small cell lung cancer (NSCLC) patients with acquired resistance to EGFR-TKI harbor the <i>EGFR</i> mutation T790M. The recent development and wide use of third-generation EGFR-TKIs targeting T790M-mutant NSCLCs have increased the importance of rebiopsy after EGFR-TKI failure. We aimed to investigate the advantages of flexible bronchoscopy as a rebiopsy method and the prevalence of and factors affecting the T790M mutation after EGFR-TKI failure. <b>Methods</b>: We investigated 139 patients who had undergone bronchoscopic rebiopsy and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) between Sep 2014 and Jul 2016. <b>Results</b>: Among the 139 patients, bronchoscopic rebiopsy yielded successful pathological diagnoses in 102 (73.4%). Among them, 41 patients with <i>EGFR</i>-mutant lung adenocarcinoma and EGFR-TKI progression were selected for an investigation of T790M mutation prevalence at rebiopsy. The initial <i>EGFR</i> mutations were exon 19 del (56.1%), L858R or L861Q (34.1%), and others (9.8%). The most common rebiopsy method was transbronchial lung biopsy (41.5%), followed by EBUS-TBNA (26.8%) and endobronchial biopsy (19.5%). The median interval to T790M emergence was the longest among cases with exon 19 deletion (14.1 months), followed by exon 21 L858R or L861Q (11.3 months) and other rare <i>EGFR</i> mutations (2.9 months). The T790M mutation was identified in 18 (43.9%) patients, and exon 19 del was the most significant factor affecting T790M mutation development (hazard ratio: 6.875, <i>P</i> = 0.014). <b>Conclusions</b>: Bronchoscopy was more useful than other rebiopsy approaches. The T790M emergence rate was highest in cases with exon 19 deletion, likely as a consequence of long-term EGFR-TKI exposure.