Comprehensive multi‐omics analysis of resectable locally advanced gastric cancer: Assessing response to neoadjuvant camrelizumab and chemotherapy in a single‐center, open‐label, single‐arm phase II trial

作者：Yuzhou Zhao, Danyang Li, Jing Zhuang, Zhimeng Li, Qingxin Xia, Zhi Li, Juan Yu, Jinbang Wang, Yong Zhang, Ke Li, Shuning Xu, Sen Li, Pengfei Ma, Yanghui Cao, Chen-Yu Liu, Chunmiao Xu, Zhentian Liu, Jinwang Wei, Chengjuan Zhang, Lei Qiao, Xuan Gao, Zhiguo Hou, Chenxuan Liu, Rongrong Zheng, Du Wang, Ying Liu · 发表于：Clinical and Translational Medicine · 年份：2024 · DOI：10.1002/ctm2.1674 · 被引用次数：21 · 研究领域：Gastric Cancer Management and Outcomes、Cancer Immunotherapy and Biomarkers、Ferroptosis and cancer prognosis

BACKGROUND: The current standard of care for locally advanced gastric cancer (GC) involves neoadjuvant chemotherapy followed by radical surgery. Recently, neoadjuvant treatment for this condition has involved the exploration of immunotherapy plus chemotherapy as a potential approach. However, the efficacy remains uncertain. METHODS: A single-arm, phase 2 study was conducted to evaluate the efficacy and tolerability of neoadjuvant camrelizumab combined with mFOLFOX6 and identify potential biomarkers of response through multi-omics analysis in patients with resectable locally advanced GC. The primary endpoint was the pathological complete response (pCR) rate. Secondary endpoints included the R0 rate, near pCR rate, progression-free survival (PFS), disease-free survival (DFS), and overall survival (OS). Multi-omics analysis was assessed by whole-exome sequencing, transcriptome sequencing, and multiplex immunofluorescence (mIF) using biopsies pre- and post-neoadjuvant therapy. RESULTS: This study involved 60 patients, of which 55 underwent gastrectomy. Among these, five (9.1%) attained a pathological complete response (pCR), and 11 (20.0%) reached near pCR. No unexpected treatment-emergent adverse events or perioperative mortality were observed, and the regimen presented a manageable safety profile. Molecular changes identified through multi-omics analysis correlated with treatment response, highlighting associations between HER2-positive and CTNNB1 mutations with treatment sensi...