Small-cell transformation of advanced non-small-cell lung cancer harboring driver mutations following tyrosine kinase inhibitor therapy: a multicenter real-world study.

Background: Tyrosine kinase inhibitors (TKIs) are a mainstay of therapy for advanced non-small-cell lung cancer (NSCLC) harboring actionable driver mutations. However, histologic transformation from NSCLC to small-cell lung cancer (SCLC) represents a particularly challenging mechanism of treatment resistance. This study aimed to characterize the incidence, timing, and clinical outcomes of SCLC transformation in this population in routine clinical practice. Methods: This multicenter real-world cohort study included consecutive patients with stage III-IV NSCLC treated at three hospitals in Sichuan Province, China, between January 2018 and December 2021. Eligible patients had pathologically confirmed NSCLC, driver mutations, baseline whole-body imaging, complete clinical data, and received TKIs. Re-biopsy was performed to evaluate histologic changes. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared with the log-rank test. Results: Among 387 enrolled patients, driver mutations included Conclusions: In this multicenter real-world cohort study of driver-mutated advanced NSCLC treated with TKIs, SCLC transformation was not rare among re-biopsied patients and occurred mainly after first-line therapy. These findings support a low threshold for repeat tissue sampling at disease progression to detect SCLC transformation and guide timely transition to SCLC-directed treatment.