P3.15-014 Case Series of Small Cell Lung Cancer Transformation as Resistance Mechanism to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor

Abstract

Patients with epidermal growth factor receptor (EGFR) mutant advanced non-small cell lung cancer (NSCLC) developed resistance to first- or second-generation EGFR-tyrosine kinase inhibitor (TKI) after 9-13 months and third-generation EGFR-TKI after 10 months, respectively. Small cell lung cancer (SCLC) transformation is a rare resistance mechanism in these patients. Tissue re-biopsy was performed in 35 patients with EGFR mutant advanced NSCLC who failed first-line EGFR-TKI; and 4 patients with acquired T790M mutant advanced NSCLC who failed third-generation EGFR-TKI, to look for SCLC transformation SCLC transformation was identified in 2 out of 35 (5.7%) patients who failed first-line EGFR-TKI and 1 out of 4 (25.0%) patients who failed third-generation EGFR-TKI. The first patient was a 70-year-old never-smoker male who was diagnosed with stage IV lung adenocarcinoma harboring exon 19 deletion mutation in April 2014. He had partial response (PR) to gefitinib 250 mg daily but developed symptomatic progressive disease (PD) after 26 months. Re-biopsy of his enlarging primary lung lesion showed SCLC transformation. The second patient was a 43-year-old never-smoker male who was diagnosed with stage IV lung adenocarcinoma harboring exon 19 deletion mutation in November 2015. He had PR to gefitinib 250 mg daily but developed symptomatic PD after 15 months. Re-biopsy of his rapidly enlarging primary lung lesion showed SCLC transformation. His plasma cell-free tumor DNA (cftDNA) was positive for T790M mutation. The third patient was a 62-year-old never-smoker female who was diagnosed with stage IV lung adenocarcinoma harboring exon 21 L858R mutation in November 2015. She had PR to gefitinib 250 mg daily but experienced symptomatic PD after 8 months’ of gefitinib therapy. Re-biopsy of her primary lung tumor revealed the presence of T790M mutation and her treatment was switched to osimertinib 80 mg daily. After an initial PR, she developed PR in the 12th month of osimertinib treatment. Biopsy from a metastatic inguinal lymph node showed SCLC. The first and second patients were given standard SCLC chemotherapy with carboplatin and etoposide but did not respond. The third patient sought treatment in another hospital. Re-biopsy is recommended in all patients with symptomatic PD while on EGFR-TKI treatment. SCLC transformation under the pressure of first, second and third-generation EGFR-TKI is an emerging challenge to the management of advanced NSCLC. Other than conventional carboplatin and etoposide chemotherapy, new treatment strategies should be explored to improve the outcome of patients who develop SCLC transformation.