Real-World EGFR T790M Testing in Advanced Non-Small-Cell Lung Cancer: A Prospective Observational Study in Japan

Introduction: Approximately one-half of patients with epidermal growth factor receptor (EGFR) mutation-positive advanced/metastatic non-small-cell lung cancer (NSCLC) develop resistance to first- or second-generation EGFR tyrosine kinase inhibitors (TKIs) due to a secondary T790M mutation. This study investigated the pattern of T790M testing after EGFR TKI treatment in a real-world setting in Japan. Method: This prospective observational study enrolled patients with EGFR mutation-positive advanced/metastatic NSCLC who reported disease progression during treatment with first- or second-generation EGFR TKIs. Data regarding sampling methods for T790M mutation testing (plasma sample, cytology or tissue biopsy) and the treatment strategies after disease progression were recorded prospectively. Results: A total of 236 patients were included in the study (female, 67.4%; median age, 73.0years), and 205 patients (86.9%) underwent rebiopsy by any of the three possible methods: plasma sampling in 137 patients (58.1%) and tissue/cytology sampling in 68 patients (28.8%) during the first rebiopsy. Overall, 80.6% of the tissue/cytology samples contained tumor cells, and 40% of these samples were positive for the T790M mutation. T790M mutations were detected in only 19.7% of plasma samples. Of the 199 patients who underwent T790M testing, 61 (30%) tested positive, and 56 (91.8%) subsequently received osimertinib. Conclusion: Among the 87% of Japanese patients who underwent rebiopsy after progressing on treatment with a first- or second-generation EGFR TKI, approximately 30% tested positive for the T790M mutation and were eligible to receive osimertinib. Although plasma sampling is non-invasive, this rebiopsy method is less sensitive for T790M detection compared with tissue or cytology sampling (UMIN identifier: UMIN000024928).