Large Cell Neuroendocrine Carcinoma Transformation as a Mechanism of Acquired Resistance to Osimertinib in Non-small Cell Lung Cancer: Case Report and Literature Review

• New metastatic sites in non-small cell lung cancer (NSCLC) patients have been shown to have the potential to transform into another histologic subtype that is different from the original histology of the patient while on treatment. • These histological transformations can indicate potential resistance mechanisms to current or prior treatments and can prompt a change in management in patients. • However, little is known about histologic transformations in NSCLC patients and what are the next steps in management. • New reports have shown that epidermal growth factor receptor tyrosine kinase inhibitors such as osimertinib can also lead to these histologic transformations in NSCLC cases and rarely to either large cell neuroendocrine carcinomas or small cell carcinoma. • This case highlights the important implications for these patients since the treatment plans are different and changes in prognosis and for clinicians to be aware of these possibilities and consider repeat biopsies and genomic testing to optimize treatment.