Long-term survival following SCLC transformation after osimertinib resistance in EGFR-mutant NSCLC: Benefit from local surgical resection and osimertinib rechallenge

Long-term survival following SCLC transformation after osimertinib resistance in EGFR-mutant NSCLC: Benefit from local surgical resection and osimertinib rechallengeTransformation to small cell lung cancer (T-SCLC) is a resistance mechanism in EGFR-mutant non-small cell lung cancer (NSCLC), primarily occurring in patients with lung adenocarcinoma harboring sensitive EGFR mutations who develop resistance after epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy.The incidence ranges from 5% to 14%, typically emerging 14-26 months (median 18 months) after EGFR-TKI treatments. 1 Most T-SCLCs retain the original lung adenocarcinoma driver mutations (∼84%-88%) while acquiring classic SCLC genetic features, such as TP53 and RB1 mutations.Existing therapeutic approaches for T-SCLC are primarily supported by evidence from retrospective studies and case reports.Chemotherapy remains the most common treatment option for T-SCLC.Although most T-SCLC cases initially respond well to etoposide-platinum combination chemotherapy, the duration of response is typically limited. 1 This case report demonstrates a viable therapeutic alternative for this patient subset, supporting the role of surgery and targeted therapy rechallenge in T-SCLC transformation.A 54-year-old female nonsmoker was referred to our hospital in April 2016 with a 2-month history of cough.On April 20, 2016, she underwent radical surgery for right lung adenocarcinoma (stage: pT3N0M0, IIB).Adjuvant chemotherapy consisting of gemcitabine (1000 mg/m 2 , intravenously, every 3 weeks) plus cisplatin (80 mg/m 2 , intravenously, every 3 weeks) was administered from May to July 2016 (4 cycles total).In December 2017, a follow-up positron emission tomography-computed tomography (PET-CT) revealed pleura and right third anterior rib metastases