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2026年8月29日星期六
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在EGFR突变NSCLC发生SCLC转化后，免疫治疗联合化疗可能改善生存：一项多中心真实世界研究

Adding immunotherapy to chemotherapy may improve survival after SCLC transformation in EGFR-mutant NSCLC: a multicenter real-world study.

期刊
Lung Cancer
PMID
42664544
原文
PubMed ↗
发布日期

作者

  • Nazan Demir — Koç University Hospital, Department of Medical Oncology, Istanbul, Turkey. Electronic address: ndemir@kuh.ku.edu.tr.
  • Cevat İlteriş Kıkılı — Koç University Hospital, Department of Medical Oncology, Istanbul, Turkey. Electronic address: ckikili@kuh.ku.edu.tr.
  • Fatih Kemik — Koç University Hospital, Department of Medical Oncology, Istanbul, Turkey. Electronic address: fkemik@kuh.ku.edu.tr.
  • Bahadır Köylü — Koç University Hospital, Department of Medical Oncology, Istanbul, Turkey. Electronic address: bkoylu@kuh.ku.edu.tr.
  • Deniz Tural — Koç University Hospital, Department of Medical Oncology, Istanbul, Turkey. Electronic address: dtural@kuh.ku.edu.tr.
  • Şahin Laçin — Koç University Hospital, Department of Medical Oncology, Istanbul, Turkey. Electronic address: salacin@kuh.ku.edu.tr.
  • Şeyda Gündüz — Koç University Hospital, Department of Medical Oncology, Istanbul, Turkey. Electronic address: segunduz@kuh.ku.edu.tr.
  • Didem Tunalı — Koç University Hospital, Department of Medical Oncology, Istanbul, Turkey. Electronic address: dtunali@kuh.ku.edu.tr.
  • Nil Molinas Mandel — American Hospital, Department of Medical Oncology, Istanbul, Turkey. Electronic address: nilm@amerikanhastanesi.org.
  • Fulden Yumuk — American Hospital, Department of Medical Oncology, Istanbul, Turkey. Electronic address: fyumuk@kuh.ku.edu.tr.
  • Mevlude Inanc — Erciyes University, Department of Medical Oncology, Kayseri, Turkey. Electronic address: mevludeinanc@erciyes.edu.tr.
  • Ayse Nuransoy Cengiz — Erciyes University, Department of Medical Oncology, Kayseri, Turkey. Electronic address: aysecengiz@erciyes.edu.tr.
  • Başak Oyan Uluç — Acıbadem University School of Medicine, Acıbadem Altunizade Hospital, Department of Medical Oncology, Istanbul, Turkey. Electronic address: basak.uluc@acibadem.com.
  • Seval Ay Ersoy — Kartal Dr Lütfi Kırdar City Hospital, Department of Medical Oncology, Istanbul, Turkey.
  • Nisanur Sarıyar Busery — Kartal Dr Lütfi Kırdar City Hospital, Department of Medical Oncology, Istanbul, Turkey.
  • Serdar Karakaya — Ankara Atatürk Sanotorium Training and Research Hospital, Department of Medical Oncology, Ankara, Turkey.
  • Dilek Erdem — Istinye University, Department of Medical Oncology, Istanbul, Turkey.
  • Orhun Akdoğan — Gazi University Faculty of Medicine Hospital, Department of Medical Oncology, Turkey.
  • Ozan Yazıcı — Gazi University Faculty of Medicine Hospital, Department of Medical Oncology, Turkey. Electronic address: ozanyazici@gazi.edu.tr.
  • Elanur Kahraman — Karadeniz Technical University Faculty of Medicine, Department of Medical Oncology, Trabzon, Turkey. Electronic address: drelanurkaraman@ktu.edu.tr.
  • İrem Bilgetekin — Memorial Ankara Hospital, Department of Medical Oncology, Ankara, Turkey.
  • Umut Demirci — Memorial Ankara Hospital, Department of Medical Oncology, Ankara, Turkey. Electronic address: umut.demirci@memorial.com.tr.
  • Hasibe Bilge Gür — Sakarya Training and Research Hospital, Department of Medical Oncology, Sakarya, Turkey.
  • İlker Nihat Ökten — Göztepe Prof. Dr. Süleyman Yalçın City Hospital , Department of Medical Oncology, Istanbul, Turkey.
  • Gökhan Karakaya — Özel ASV Yasam Hospital, Department of Medical Oncology, Antalya, Turkey.
  • Oğuzhan Yıldız — Necmettin Erbakan University School of Medicine, Department of Medical Oncology, Konya, Turkey.
  • Melek Karakurt Eryılmaz — Necmettin Erbakan University School of Medicine, Department of Medical Oncology, Konya, Turkey.
  • Kübra Canaslan — Dokuz Eylül University, Department of Medical Oncology, İzmir, Turkey.
  • Mustafa Seyyar — Gaziantep City Hospital, Department of Medical Oncology, Gaziantep, Turkey.
  • Muhammet Ali Kaplan — Dicle University, Department of Medical Oncology, Diyarbakır, Turkey.
  • Erdem Çubukçu — Uludağ University Hospital, Department of Medical Oncology, Bursa, Turkey. Electronic address: erdemcubukcu@uludag.edu.tr.
  • Gül Akın — Uludağ University Hospital, Department of Medical Oncology, Bursa, Turkey. Electronic address: gulakin@uludag.edu.tr.
  • Mustafa Ersoy — Kütahya Health Sciences University, Department of Medical Oncology, Kütahya, Turkey. Electronic address: mustafa.ersoy@ksbu.edu.tr.
  • Ahmet Taner Sümbül — Medical Park Seyhan Hospital, Department of Medical Oncology, Adana, Turkey.
  • Hakan Özçelik — Medipol University Hospital, Department of Medical Oncology, Istanbul, Turkey.
  • Dilruba İlayda Özel Bozdağ — Gülhane Training and Research Hospital, Department of Medical Oncology, Ankara, Turkey.
  • Ebru Çiçek — Istanbul University Cerrahpaşa Faculty of Medicine, Department of Medical Oncology, Istanbul, Turkey.
  • Ülviye Oflas — Düzce Ataturk State Hospital, Department of Medical Oncology, Düzce, Turkey.
  • Fatma Paksoy Turkoz — Bahcesehir University Faculty of Medicine, Department of Medical Oncology, Istanbul, Turkey. Electronic address: fatma.paksoyturkoz@bau.edu.tr.
  • Duygu Bayır Garbioğlu — Osmangazi University Faculty of Medicine, Department of Medical Oncology, Eskişehir, Turkey.
  • Fatih Selçukbiricik — Koç University Hospital, Department of Medical Oncology, Istanbul, Turkey. Electronic address: fselcukbiricik@kuh.ku.edu.tr.

作者单位

  • Koç University Hospital, Department of Medical Oncology, Istanbul, Turkey. Electronic address: ndemir@kuh.ku.edu.tr.
  • Koç University Hospital, Department of Medical Oncology, Istanbul, Turkey. Electronic address: ckikili@kuh.ku.edu.tr.
  • Koç University Hospital, Department of Medical Oncology, Istanbul, Turkey. Electronic address: fkemik@kuh.ku.edu.tr.
  • Koç University Hospital, Department of Medical Oncology, Istanbul, Turkey. Electronic address: bkoylu@kuh.ku.edu.tr.
  • Koç University Hospital, Department of Medical Oncology, Istanbul, Turkey. Electronic address: dtural@kuh.ku.edu.tr.
  • Koç University Hospital, Department of Medical Oncology, Istanbul, Turkey. Electronic address: salacin@kuh.ku.edu.tr.
  • Koç University Hospital, Department of Medical Oncology, Istanbul, Turkey. Electronic address: segunduz@kuh.ku.edu.tr.
  • Koç University Hospital, Department of Medical Oncology, Istanbul, Turkey. Electronic address: dtunali@kuh.ku.edu.tr.
  • American Hospital, Department of Medical Oncology, Istanbul, Turkey. Electronic address: nilm@amerikanhastanesi.org.
  • American Hospital, Department of Medical Oncology, Istanbul, Turkey. Electronic address: fyumuk@kuh.ku.edu.tr.
  • Erciyes University, Department of Medical Oncology, Kayseri, Turkey. Electronic address: mevludeinanc@erciyes.edu.tr.
  • Erciyes University, Department of Medical Oncology, Kayseri, Turkey. Electronic address: aysecengiz@erciyes.edu.tr.
  • Acıbadem University School of Medicine, Acıbadem Altunizade Hospital, Department of Medical Oncology, Istanbul, Turkey. Electronic address: basak.uluc@acibadem.com.
  • Kartal Dr Lütfi Kırdar City Hospital, Department of Medical Oncology, Istanbul, Turkey.
  • Ankara Atatürk Sanotorium Training and Research Hospital, Department of Medical Oncology, Ankara, Turkey.
  • Istinye University, Department of Medical Oncology, Istanbul, Turkey.
  • Gazi University Faculty of Medicine Hospital, Department of Medical Oncology, Turkey.
  • Gazi University Faculty of Medicine Hospital, Department of Medical Oncology, Turkey. Electronic address: ozanyazici@gazi.edu.tr.
  • Karadeniz Technical University Faculty of Medicine, Department of Medical Oncology, Trabzon, Turkey. Electronic address: drelanurkaraman@ktu.edu.tr.
  • Memorial Ankara Hospital, Department of Medical Oncology, Ankara, Turkey.
  • Memorial Ankara Hospital, Department of Medical Oncology, Ankara, Turkey. Electronic address: umut.demirci@memorial.com.tr.
  • Sakarya Training and Research Hospital, Department of Medical Oncology, Sakarya, Turkey.
  • Göztepe Prof. Dr. Süleyman Yalçın City Hospital , Department of Medical Oncology, Istanbul, Turkey.
  • Özel ASV Yasam Hospital, Department of Medical Oncology, Antalya, Turkey.
  • Necmettin Erbakan University School of Medicine, Department of Medical Oncology, Konya, Turkey.
  • Dokuz Eylül University, Department of Medical Oncology, İzmir, Turkey.
  • Gaziantep City Hospital, Department of Medical Oncology, Gaziantep, Turkey.
  • Dicle University, Department of Medical Oncology, Diyarbakır, Turkey.
  • Uludağ University Hospital, Department of Medical Oncology, Bursa, Turkey. Electronic address: erdemcubukcu@uludag.edu.tr.
  • Uludağ University Hospital, Department of Medical Oncology, Bursa, Turkey. Electronic address: gulakin@uludag.edu.tr.
  • Kütahya Health Sciences University, Department of Medical Oncology, Kütahya, Turkey. Electronic address: mustafa.ersoy@ksbu.edu.tr.
  • Medical Park Seyhan Hospital, Department of Medical Oncology, Adana, Turkey.
  • Medipol University Hospital, Department of Medical Oncology, Istanbul, Turkey.
  • Gülhane Training and Research Hospital, Department of Medical Oncology, Ankara, Turkey.
  • Istanbul University Cerrahpaşa Faculty of Medicine, Department of Medical Oncology, Istanbul, Turkey.
  • Düzce Ataturk State Hospital, Department of Medical Oncology, Düzce, Turkey.
  • Bahcesehir University Faculty of Medicine, Department of Medical Oncology, Istanbul, Turkey. Electronic address: fatma.paksoyturkoz@bau.edu.tr.
  • Osmangazi University Faculty of Medicine, Department of Medical Oncology, Eskişehir, Turkey.
  • Koç University Hospital, Department of Medical Oncology, Istanbul, Turkey. Electronic address: fselcukbiricik@kuh.ku.edu.tr.

摘要

中文

小细胞肺癌（SCLC）组织学转化是EGFR突变非小细胞肺癌（NSCLC）对EGFR酪氨酸激酶抑制剂（TKI）治疗的一种侵袭性耐药机制。关于这一人群的真实世界数据仍然有限。我们在26个肿瘤中心进行了一项多中心回顾性队列研究（2016-2025年）。纳入经组织学确诊为EGFR突变NSCLC且活检证实发生SCLC转化的患者。主要终点包括一线EGFR-TKI治疗期间的PFS（PFS1）、转化时间（TTT）、转化后PFS（PFS2）、自转移诊断起的OS（OS-1）、转化后生存（OS-2）以及自初始NSCLC诊断起的OS（OS-3）。采用Kaplan-Meier和Cox回归分析评估生存。共纳入59例患者（中位年龄57.8岁；52.5%为男性；外显子19缺失76.3%）。中位PFS1为14.0个月（95% CI，11.3-16.7）；中位TTT为22.0个月（范围3-110）。转化后，54例（91.5%）接受了全身治疗：37例（68.5%）接受卡铂联合依托泊苷（CE）单药治疗，16例（29.6%）接受CE联合免疫治疗（atezolizumab、durvalumab或durvalumab联合奥希替尼）。CE单药组的ORR为37.8%，CE联合免疫治疗组为71.4%；中位PFS2为5.0个月（95% CI，3.5-6.5）。中位OS-1为38.0个月（95% CI，32.0-53.0）。总体中位OS-2为11.0个月（95% CI，7.5-14.5），CE联合免疫治疗组显著长于CE单药组（17.0 vs 9.0个月；log-rank p=0.026；HR 0.327，95% CI 0.139-0.767）。中位OS-3为41.1个月。在这个大型多中心队列中，将免疫检查点抑制剂（ICIs）添加到CE方案中与转化后生存改善相关，这挑战了先前关于免疫治疗在该情况下无效的证据。在EGFR-TKI治疗进展时进行系统性再活检对于确认转化和指导治疗至关重要。需要前瞻性生物标志物驱动的研究。

English

Histologic transformation to small-cell lung cancer (SCLC) is an aggressive resistance mechanism to EGFR tyrosine kinase inhibitor (TKI) therapy in EGFR-mutant non-small cell lung cancer (NSCLC). Real-world data on this population remain limited. We conducted a multicenter retrospective cohort study across 26 oncology centers (2016-2025). Patients with histologically confirmed EGFR-mutant NSCLC and biopsy-proven SCLC transformation were included. Primary endpoints included PFS during first-line EGFR-TKI therapy (PFS1), time to transformation (TTT), PFS after transformation (PFS2), overall survival from metastatic diagnosis (OS-1), post-transformation survival (OS-2), and overall survival from initial NSCLC diagnosis (OS-3). Survival was assessed with Kaplan-Meier and Cox regression analyses. A total of 59 patients were included (median age 57.8 years; 52.5 % male; exon 19 deletion 76.3 %). Median PFS1 was 14.0 months (95 % CI, 11.3-16.7); median TTT was 22.0 months (range, 3-110). Following transformation, 54 patients (91.5 %) received systemic therapy: carboplatin plus etoposide (CE) alone in 37 (68.5 %) and CE plus immunotherapy (atezolizumab, durvalumab, or durvalumab plus osimertinib) in 16 (29.6 %). ORR was 37.8 % with CE alone versus 71.4 % with CE plus immunotherapy; median PFS2 was 5.0 months (95 % CI, 3.5-6.5). Median OS-1 was 38.0 months (95 % CI, 32.0-53.0). Median OS-2 was 11.0 months (95 % CI, 7.5-14.5) overall, and significantly longer with CE plus immunotherapy versus CE alone (17.0 vs. 9.0 months; log-rank p = 0.026; HR 0.327, 95 % CI 0.139-0.767). Median OS-3 was 41.1 months. In this large multicenter cohort, adding immune checkpoint inhibitors (ICIs) to CE was associated with improved post-transformation survival, challenging prior evidence of immunotherapy inefficacy in this setting. Systematic re-biopsy at progression on EGFR-TKI therapy is essential to confirm transformation and guide treatment. Prospective biomarker-driven studies are warranted.

分类与指标

研究类型
临床研究
病种
肺癌
JCR 分区
Q1
影响因子
5.3
新锐分区
2区