Long-term Disease Control After Probable Endobronchial Small-cell Transformation During Osimertinib Therapy for EGFR-mutant Lung Adenocarcinoma

Osimertinib provides durable progression-free survival in EGFR-mutant non-small-cell lung cancer (NSCLC), but acquired resistance is inevitable. Histologic transformation to small-cell lung cancer (SCLC) is a recognized resistance mechanism, typically presenting with widespread metastatic disease and a poor prognosis. Optimal post-transformation treatment strategies have not been established.

We report a patient with EGFR exon 19 deletion-positive lung adenocarcinoma who achieved prolonged disease control on osimertinib for mediastinal lymph node recurrence before developing a new endobronchial lesion in the left main bronchus. Rigid bronchoscopic resection and temporary airway stenting relieved the critical obstruction. Pathologic examination confirmed SCLC, and immunohistochemistry of both the initial adenocarcinoma and the endobronchial lesion demonstrated concordant p53 over-expression and loss of Rb expression, supporting a clinical diagnosis of probable histologic transformation. The patient was bridged to sequential chemoradiotherapy, followed by successful stent removal and the resumption of osimertinib, resulting in long-term disease control exceeding four years.

An individualized, multidisciplinary approach comprising rigid bronchoscopic resection, temporary airway stenting, chemoradiotherapy, and osimertinib resumption may achieve prolonged disease control in locoregionally confined SCLC arising during osimertinib therapy. Further case accumulation is warranted to establish optimal treatment strategies.