Chen Ching-Yi, Ko How-Wen, Hu Po-Wei, Chang Cheng-Yu, Chen Chung-Yu, Chang Shih-Chieh, Chiu Yu-Chi, Wei Yu-Feng
Division of Chest Medicine, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
College of Medicine, I-Shou University, Kaohsiung, Taiwan.
Lung Cancer (Auckl). 2025 Apr 12;16:25-37. doi: 10.2147/LCTT.S516527. eCollection 2025.
In epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients treated with EGFR-tyrosine kinase inhibitors (TKIs), transformation to small-cell lung cancer (SCLC) is associated with poor outcomes, and the optimal treatment strategy is unclear. This study aimed to investigate the clinical factors and treatments associated with outcomes in this group.
This retrospective multicenter study enrolled patients with SCLC transformed from advanced NSCLC after progression on EGFR-TKI treatment. We analyzed clinical and demographic characteristics, first-line EGFR-TKI treatments, and subsequent regimens to identify factors associated with clinical outcomes.
Twenty-seven patients diagnosed with SCLC transformation after EGFR-TKI therapy between 2018 and 2023 were enrolled, most of whom had an EGFR exon 19 deletion (67%). The subsequent treatment regimens included traditional chemotherapy (CT) in 12 patients (44%), combined CT/EGFR-TKI in 10 patients (37%), and combined CT/immunotherapy in 5 patients (19%). The median progression-free survival (PFS) with first-line EGFR-TKI treatment, subsequent SCLC treatment, and overall survival (OS) were 16.1 months, 6.4 months, and 39.5 months, respectively. The overall response rate (ORR), disease control rate (DCR), and median PFS for subsequent treatments were 38.5%, 69.2%, and 6.4 months, respectively. The DCRs for subsequent CT, CT/TKI, and CT/immunotherapy were 41.7%, 88.9%, and 100%, respectively. ORR and PFS were higher in the CT/TKI (44.4% and 7.2 months) and CT/immunotherapy (80.0% and 11.3 months) groups compared to CT (16.7% and 3.7 months), but these differences were not statistically significant. Univariate and multivariate analyses showed no significant differences in PFS and OS among treatments.
In patients with SCLC transformed from advanced NSCLC after EGFR-TKI treatment, adding immunotherapy and EGFR-TKI to CT improved DCR and showed trends in ORR and PFS, but did not provide an OS benefit. More prospective studies with varied therapeutic approaches are needed to confirm these findings.
在接受表皮生长因子受体（EGFR）-酪氨酸激酶抑制剂（TKIs）治疗的EGFR突变型非小细胞肺癌（NSCLC）患者中，转化为小细胞肺癌（SCLC）与不良预后相关，最佳治疗策略尚不清楚。本研究旨在调查该组患者与预后相关的临床因素和治疗方法。
这项回顾性多中心研究纳入了在EGFR-TKI治疗进展后从晚期NSCLC转化为SCLC的患者。我们分析了临床和人口统计学特征、一线EGFR-TKI治疗以及后续治疗方案，以确定与临床结局相关的因素。
纳入了2018年至2023年间27例在EGFR-TKI治疗后被诊断为SCLC转化的患者，其中大多数患者存在EGFR外显子19缺失（67%）。后续治疗方案包括12例患者（44%）接受传统化疗（CT），10例患者（37%）接受CT/EGFR-TKI联合治疗，5例患者（19%）接受CT/免疫治疗联合治疗。一线EGFR-TKI治疗的中位无进展生存期（PFS）、后续SCLC治疗的中位PFS以及总生存期（OS）分别为16.1个月、6.4个月和39.5个月。后续治疗的总缓解率（ORR）、疾病控制率（DCR）和中位PFS分别为38.5%、69.2%和6.4个月。后续CT、CT/TKI和CT/免疫治疗的DCR分别为41.7%、88.9%和100%。与CT组（16.7%和3.7个月）相比，CT/TKI组（44.4%和7.2个月）和CT/免疫治疗组（80.0%和11.3个月）的ORR和PFS更高，但这些差异无统计学意义。单因素和多因素分析显示，各治疗组之间的PFS和OS无显著差异。
在EGFR-TKI治疗后从晚期NSCLC转化为SCLC的患者中，在CT基础上加用免疫治疗和EGFR-TKI可提高DCR，并在ORR和PFS方面呈现趋势，但未带来OS获益。需要更多采用不同治疗方法的前瞻性研究来证实这些发现。
