Regorafenib plus toripalimab in patients with metastatic colorectal cancer: a phase Ib/II clinical trial and gut microbiome analysis.

• 影响指数: 16.988
• 发表时间: Sep 2021 21
• 来源期刊: Cell Rep Med
• DOI: 10.1016/j.xcrm.2021.100383
• PMID: 34622226
• 文章类型: Journal Article
• 作者列表: Wang F,He MM,Yao YC,Zhao X,Wang ZQ,Jin Y,Luo HY,Li JB,Wang FH,Qiu MZ,Lv ZD,Wang DS,Li YH,Zhang DS,Xu RH

关键词: colorectal cancer; immunotherapy; microbiome; programmed cell death protein 1; regorafenib; toripalimab

Abstract

This is a phase Ib/II study of regorafenib plus toripalimab for colorectal cancer. The objective response rate (ORR) is 15.2% and the disease control rate is 36.4% in evaluable patients with recommended phase II dose (80 mg regorafenib plus toripalimab). The median progression-free survival (PFS) and the median overall survival are 2.1 months and 15.5 months, respectively. Patients with liver metastases have lower ORR than those without (8.7% versus 30.0%). All patients (3/3) with lung-only metastasis respond, whereas no patients (0/4) with liver-only metastasis respond. 94.9% and 38.5% of patients have grade 1 and grade 3 treatment-related adverse events, respectively. Gut microbiome analysis of the baseline fecal samples shows significantly increased relative abundance and positive detection rate of Fusobacterium in non-responders than responders. Patients with high-abundance Fusobacterium have shorter PFS than those with low abundance (median PFS = 2.0 versus 5.2 months; p = 0.002).