Scholarlink

<p>The phase 3 IMpower150 trial in treatment-naïve patients with metastatic non-small-cell lung cancer (NSCLC) demonstrates significantly longer progression-free (PFS) and overall survival (OS) with first-line atezolizumab (anti-PD-L1)-bevacizumab (anti-VEGF)-carboplatin-paclitaxel (ABCP) than with bevacizumab-carboplatin-paclitaxel (BCP). We characterise four molecular NSCLC subtypes identified by unsupervised clustering of transcriptomes of 564 pre-treatment primary tumour samples from IMpower150 using non-negative matrix factorization (NMF1-4). Each subtype has distinct tumour PD-L1 expression levels, epithelial characteristics, immune composition, and treatment outcomes. Both NMF2 (enriched in tumour proliferation signal, macrophages, and monocytes) and NMF4 (enriched in B cells and T cells) have elevated tumour PD-L1 expression. Of these two, only NMF4 demonstrates PFS and OS benefits with ABCP versus either BCP or atezolizumab-carboplatin-paclitaxel (ACP). Patients with NMF1 (enriched in basal and squamous-like cells) have improved outcomes on ABCP compared with ACP or BCP; those with NMF3 (enriched in adenocarcinoma signatures) show similar outcomes among treatments. These insights could help inform individualised first-line treatment for metastatic NSCLC.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Non-small cell lung cancer molecular subtypes and vulnerability to immunotherapy treatment combinations

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月3日

查看全文
  • Tianshi Lu,
  • Habib Hamidi,
  • Mark A. Socinski,
  • Martin Reck,
  • Federico Cappuzzo,
  • Fabrice Barlesi,
  • Robert M. Jotte,
  • Sören Müller,
  • Aditi Qamra,
  • Assaf Amitai,
  • Xiangnan Guan,
  • Eloisa Fuentes,
  • Hartmut Koeppen,
  • Jennifer M. Giltnane,
  • David S. Shames,
  • Marcus Ballinger,
  • Meng Xiao He,
  • Yulei Wang,
  • Minu K. Srivastava,
  • Barzin Y. Nabet

摘要

The phase 3 IMpower150 trial in treatment-naïve patients with metastatic non-small-cell lung cancer (NSCLC) demonstrates significantly longer progression-free (PFS) and overall survival (OS) with first-line atezolizumab (anti-PD-L1)-bevacizumab (anti-VEGF)-carboplatin-paclitaxel (ABCP) than with bevacizumab-carboplatin-paclitaxel (BCP). We characterise four molecular NSCLC subtypes identified by unsupervised clustering of transcriptomes of 564 pre-treatment primary tumour samples from IMpower150 using non-negative matrix factorization (NMF1-4). Each subtype has distinct tumour PD-L1 expression levels, epithelial characteristics, immune composition, and treatment outcomes. Both NMF2 (enriched in tumour proliferation signal, macrophages, and monocytes) and NMF4 (enriched in B cells and T cells) have elevated tumour PD-L1 expression. Of these two, only NMF4 demonstrates PFS and OS benefits with ABCP versus either BCP or atezolizumab-carboplatin-paclitaxel (ACP). Patients with NMF1 (enriched in basal and squamous-like cells) have improved outcomes on ABCP compared with ACP or BCP; those with NMF3 (enriched in adenocarcinoma signatures) show similar outcomes among treatments. These insights could help inform individualised first-line treatment for metastatic NSCLC.