Kuang Linwu, Wang Peng, Zhou Lin, Li Yangkai
Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Anticancer Drugs. 2025 Mar 1;36(3):253-259. doi: 10.1097/CAD.0000000000001686. Epub 2025 Jan 8.
Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) effectively treat EGFR-mutant lung adenocarcinoma, demonstrating initial efficacy but eventually leading to acquired resistance. Small cell transformation is a rare resistance mechanism to EGFR-TKIs in lung adenocarcinoma, which can complicate clinical diagnosis and treatment. We present a patient with lung adenocarcinoma who underwent a prior pneumonectomy and adjuvant chemotherapy and was treated with osimertinib after the recurrence of lung cancer. Small cell transformation occurred approximately 20 months after starting osimertinib treatment. After this transformation, the patient underwent lung radiotherapy and cisplatin-etoposide chemotherapy, which stabilized the disease. Following the confirmation of small cell lung cancer (SCLC) via thyroid puncture, treatments with irinotecan, irinotecan plus atezolizumab, thyroid radiotherapy, adrenal radiotherapy, and head radiotherapy were sequentially administered, yet the disease continued to progress. The patient succumbed to the disease in May 2023 because of progression and organ failure, with an overall survival of 52.7 months, including 16 months post small cell transformation. This case highlights the possibility of osimertinib causing lung adenocarcinoma to transform into SCLC and underscores rebiopsies' importance in identifying resistance mechanisms to EGFR-TKIs. Increased levels of neuron-specific enolase and pro-gastrin releasing peptide can signal early transformation into SCLC.
表皮生长因子受体（EGFR）-酪氨酸激酶抑制剂（TKIs）可有效治疗EGFR突变型肺腺癌，显示出初始疗效，但最终会导致获得性耐药。小细胞转化是肺腺癌中对EGFR-TKIs罕见的耐药机制，可使临床诊断和治疗复杂化。我们报告了1例肺腺癌患者，该患者曾接受肺切除术和辅助化疗，肺癌复发后接受奥希替尼治疗。在开始奥希替尼治疗约20个月后发生了小细胞转化。转化后，患者接受了肺部放疗和顺铂-依托泊苷化疗，病情得到稳定。经甲状腺穿刺确诊为小细胞肺癌（SCLC）后，依次给予伊立替康、伊立替康联合阿替利珠单抗、甲状腺放疗、肾上腺放疗和头部放疗，但病情仍持续进展。该患者于2023年5月因病情进展和器官衰竭死亡，总生存期为52.7个月，其中小细胞转化后生存16个月。本病例突出了奥希替尼导致肺腺癌转化为SCLC的可能性，并强调了再次活检在确定EGFR-TKIs耐药机制中的重要性。神经元特异性烯醇化酶和胃泌素释放肽前体水平升高可能提示早期转化为SCLC。
