Catania C, Liu S V, Garassino M, Delmonte A, Scotti V, Cappuzzo F, Genova C, Russo A, Russano M, Bennati C, Colantonio I, Martini S, Pino M, Conforti F, Pala L, Muti G, Citarella F, Olmetto E, Esposito A, Cascetta P, Di Lello A, De Pas T
Division of Oncology, Humanitas Gavazzeni, Bergamo, Italy; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.
Division of Hematology and Oncology, Georgetown University, Washington, USA.
ESMO Open. 2025 Jun 24;10(7):105326. doi: 10.1016/j.esmoop.2025.105326.
Histological transformation to small-cell lung cancer (SCLC) is an under-recognized but clinically relevant mechanism of resistance in epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC). While platinum-based chemotherapy (CT) has emerged as standard treatment after small-cell transformation, optimal treatment strategies are not defined, particularly with regard to the role of immune checkpoint inhibitors (ICIs) or continuation of EGFR-tyrosine kinase inhibitors (TKIs).
We conducted an international, retrospective, observational study on patients with EGFR-mutated NSCLC that transformed to SCLC, focusing on treatment and outcomes.
Twenty-five patients across 11 centers were included. Twenty-four changed systemic treatment following SCLC transformation: CT (12 patients), CT plus EGFR-TKI (5 patients), CT plus ICI (6 patients), or CT plus ICI plus EGFR-TKI (1 patient). Median follow-up was 9 months (range 1-45 months). All patients experienced relapse with a median progression-free survival of 2 months [95% confidence interval (CI) 2-3 months] and 23 patients died, with a median overall survival (OS) of 9 months (95% CI 7-16 months). Median OS was comparable between patients treated with CT alone [9.5 months; 95% CI 5 months-not reached (NR)], CT plus EGFR-TKI (8 months; 95% CI 8 months-NR), and CT plus ICI (10 months; 95% CI 7 months-NR). Three patients survived >24 months from SCLC transformation; these patients were treated with CT alone (one patient), CT plus EGFR-TKI (one patient), and CT plus ICI and EGFR-TKI (one patient). OS was longer if SCLC transformation occurred >12 months from initial NSCLC diagnosis (19 patients) versus those with transformation within 12 months (6 patients): 31 versus 8 months (P < 0.001).
The prognosis of patients with transformed SCLC remains poor, with only a minority achieving meaningful survival. Survival was similar in patients treated with CT alone or with the addition of ICI or EGFR-TKI. A time interval >12 months between NSCLC diagnosis and SCLC transformation was associated with longer survival and may reflect a different biology than early transformation.
组织学转化为小细胞肺癌（SCLC）是表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）中一种未被充分认识但具有临床相关性的耐药机制。虽然铂类化疗（CT）已成为小细胞转化后的标准治疗方法，但最佳治疗策略尚未明确，特别是关于免疫检查点抑制剂（ICI）的作用或EGFR酪氨酸激酶抑制剂（TKI）的继续使用。
我们对转化为SCLC的EGFR突变NSCLC患者进行了一项国际、回顾性、观察性研究，重点关注治疗和结果。
纳入了11个中心的25例患者。24例在SCLC转化后改变了全身治疗：CT（12例患者）、CT加EGFR-TKI（5例患者）、CT加ICI（6例患者）或CT加ICI加EGFR-TKI（1例患者）。中位随访时间为9个月（范围1 - 45个月）。所有患者均复发，中位无进展生存期为2个月[95%置信区间（CI）2 - 3个月]，23例患者死亡，中位总生存期（OS）为9个月（95%CI 7 - 16个月）。单独接受CT治疗的患者[9.5个月；95%CI 5个月 - 未达到（NR）]、CT加EGFR-TKI治疗的患者（8个月；95%CI 8个月 - NR）和CT加ICI治疗的患者（10个月；95%CI 7个月 - NR）的中位OS相当。3例患者自SCLC转化后存活>24个月；这些患者分别接受单独CT治疗（1例患者）、CT加EGFR-TKI治疗（1例患者）和CT加ICI及EGFR-TKI治疗（1例患者）。与初始NSCLC诊断后12个月内发生SCLC转化的患者（6例）相比，若SCLC转化发生在初始NSCLC诊断>12个月后（19例），OS更长：31个月对8个月（P < 0.001）。
转化型SCLC患者的预后仍然很差，只有少数患者获得有意义的生存期。单独接受CT治疗或联合ICI或EGFR-TKI治疗的患者生存期相似。NSCLC诊断与SCLC转化之间的时间间隔>12个月与更长的生存期相关，可能反映出与早期转化不同的生物学特性。
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