Recurrence as a small cell lung cancer transformation in a resected stage IIIA EGFR-mutated non-small cell lung cancer treated with adjuvant osimertinib: a case report

Background: Based on improvements in recurrence-free and overall survival, osimertinib is now widely used as an adjuvant treatment in stage II-IIIA non-small cell lung cancer (NSCLC) presenting with a common epithelial growth factor receptor (EGFR) mutation. Histological transformation is a wellknown resistance mechanism to osimertinib in EGFR-mutated metastatic NSCLC, but we currently have insufficient data on recurrence mechanisms in the adjuvant context. We present here the case of a patient treated with adjuvant osimertinib and presenting a small cell lung cancer (SCLC) transformation as a recurrence. Case Description: A 54-year-old man, never-smoker and with no previous medical history, underwent right superior lobectomy with lymph node resection for a pT3N1M0 [stage IIIA, tumor-node-metastasis (TNM) 8th edition] adenocarcinoma. Programmed death-ligand 1 (PD-L1) negative with an EGFR exon 19 deletion. The patient received 4 cycles of adjuvant chemotherapy before starting adjuvant osimertinib 80 mg. After 35 months of adjuvant osimertinib the patient had a local recurrence and the re biopsy showed an SCLC transformation, underlining the importance of careful surveillance and biopsy at the time of recurrence in EGFR-mutated NSCLC. Conclusions: This case report provides evidence of SCLC transformation while on adjuvant osimertinib, in a pT3N1 EGFR, RB1 and TP53-mutated pulmonary adenocarcinoma. This highlights the importance of biopsy on recurrence and the transformation potential of the EGFR, RB1 and TP53-mutated adenocarcinomas.