Histological transformation from non-small cell lung cancer to small cell lung cancer in patients with osimertinib treatment failure

Histological transformation of NSCLC with EGFR mutations is a mechanism of an acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). The aim of the study is to analyze the clinical features of a patient diagnosed with advanced NSCLC, as well as the mechanism of histological transformation to small cell lung cancer (SCLC) after osimertinib treatment. In a 59-year-old non-smoking, female patient imaging tests showed the presence of a tumors in the left lung and a metastatic lesion in the right cerebellar hemisphere. The bronchofiberoscopy was performed and the histopathological result indicated adenocarcinoma. In this material, deletion in exon 19 of EGFR gene was detected. The treatment started with stereotactic radiotherapy of the central nervous system (CNS), and then the patient was qualified for treatment with osimertinib. During the therapy, adverse effects of osimertinib were observed in the form of hepatotoxicity and interstitial pneumonia. Initially, the disease remission and then stabilization were noted, but after 12 months the progression occurred. The material collected during the second bronchoscopy confirmed new recognition — neuroendocrine small cell lung cancer (SCLC) with endured presence of deletion in exon 19 of EGFR gene. The patient was qualified for second-line chemotherapy with cisplatin and etoposide. Early treatment tolerance was good and partial response was noted. It should be emphasized that the transformed tumor retained the original EGFR mutation, which confirms that the histological transformation was an evolution from the primary tumor. The re-biopsy should always be considered in NSCLC patients when EGFR-TKIs therapy is ineffective, in order to determine resistance mechanisms and to select the right therapeutic strategy.