Real‐world data on efficacy and safety of osimertinib in non‐small cell lung cancer patients with EGFR T790M mutation detected by first and repeat rebiopsy

Abstract

BackgroundOsimertinib could effectively target epidermal growth factor receptor (EGFR) T790M resistance mutations in non‐small cell lung cancer (NSCLC), indicating that rebiopsy may be particularly important. However, the clinical benefit of repeat rebiopsy in T790M‐negative patients with NSCLC detected by the first rebiopsy is still unclear, and data on the efficacy and safety of osimertinib in patients with NSCLC who are T790M‐positive patients on a repeat rebiopsy remain rare.MethodsWe retrospectively collected the clinical data of advanced NSCLC patients with common EGFR mutation who were treated with 1/2‐generation (1/2G) EGFR–tyrosine kinase inhibitors (TKIs) in first‐line therapy in our center from January 2018 to December 2020. The detection rate of T790M by first and repeat rebiopsy was recorded, and we also analyzed the efficacy and safety of osimertinib for T790M‐positive patients.ResultsAmong 190 common EGFR‐mutant patients who received 1/2G EGFR–TKIs with advanced NSCLC in the first‐line treatment, 141 patients developed progressive disease. In total, 110 of 141 accepted the first rebiopsy, with a T790M prevalence of 50.9% (56/110). In total, 43 T790M‐positive patients who received osimertinib were included in first rebiopsy group. Of 54 T790M‐negative patients detected by the first rebiopsy, 28 underwent repeated rebiopsy in subsequent clinical treatment, and 10 (35.7%) T790M‐positive cases were confirmed. In total, eight T790M‐positive patients treated with osimertinib were included in repeat rebiopsy group. Overall, 66 (60%) of 110 patients acquired a T790M mutation. In patients with the T790M mutation discovered by the first and repeat rebiopsy, osimertinib resulted in median progression‐free survival of 7 (95% confidence interval [CI]: 5.3–8.7) and 6 (95% CI: 4.7–7.3) months, respectively (p = .656). The median overall survival since osimertinib initiation for T790M‐positive patients at first rebiopsy was 20 (95% CI: 15.1–24.9) months and 19 (95% CI: 16.9–21.1) months, for those at repeated rebiopsy (p = .888). Adverse events of grade 3 or higher were similar in the two groups (25.6% vs. 12.5%, p = .616). There was no treatment‐related death in the two groups.ConclusionsRepeat rebiopsy can increase the T790M mutation positivity rate. Osimertinib showed similar efficacy and safety in T790M‐positive patients whether detected by the first or repeat rebiopsy.

Re‐re‐biopsy? How much tumor is enough in the era of precision oncology?

“…They assessed patients who progressed on a 1G/2G EGFR TKI and compared those who received osimertinib after their first re-biopsy demonstrated T790M mutation versus those who received osimertinib after a repeat re-biopsy following another therapy. 13 They demonstrated the potential benefits of re-biopsy in this population.…”

“…They reported their findings on the efficacy and safety of osimertinib in NSCLC patients with an EGFR T790M mutation, depending on when this mutation was detected. They assessed patients who progressed on a 1G/2G EGFR TKI and compared those who received osimertinib after their first re‐biopsy demonstrated T790M mutation versus those who received osimertinib after a repeat re‐biopsy following another therapy 13 . They demonstrated the potential benefits of re‐biopsy in this population.…”