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Background  Indication for treatment with osimertinib after first/second generation (1/2G) epidermal growth factor receptor‐tyrosine kinase inhibitor (EGFR‐TKI) resistance depends on T790M mutation detected by rebiopsy. The aim of our study was to analyze the data on clinical practice at our hospital where histological rebiopsy is actively carried out multiple times.    Methods  We retrospectively reviewed our electronic medical records of  EGFR ‐mutant non‐small cell lung cancer (NSCLC) patients to examine clinical rebiopsy situation, T790M detection rate, osimertinib introduction rate and associated outcomes.    Results  Among 95 patients with  EGFR ‐mutant NSCLC, 72 patients received 1/2G EGFR‐TKIs. Of 60 with progressive disease on 1/2G EGFR‐TKIs, 50 (83%) underwent rebiopsy. T790M was detected in 40 (80%) of 50, resulting in a 79% osimertinib introduction rate, as one patient refused osimertinib. T790M was detected by first rebiopsy in 18 (36%) of 50 patients, and by second or subsequent rebiopsy in 22 (44%). Median time to treatment failure of T790M‐positive patients at first rebiopsy was 22.6 (95% confidence interval [CI]: 10.2–32.8) months, and those at multiple repeated rebiopsy was 20.9 (95% CI: 8.6–not reached) months ( p  = 0.64). Median overall survival (OS) in osimertinib introduced group was 92.5 (95% CI: 62.9–not reached), while in nonosimertinib median OS was 39.0 months (95% CI: 22.2–not reached) ( p  = 0.04).    Conclusions  T790M detection rate was increased by multiple repeated rebiopsy, achieving a higher osimertinib introduction rate. This higher introduction rate could contribute to better prognosis of  EGFR ‐mutant NSCLC patients.

Higher osimertinib introduction rate achieved by multiple repeated rebiopsy after acquired resistance to first/second generation EGFR‐TKIs