Regorafenib plus toripalimab in patients with metastatic colorectal cancer: a phase Ib/II clinical trial and gut microbiome analysis.
Regorafenib plus toripalimab in patients with metastatic colorectal cancer: a phase Ib/II clinical trial and gut microbiome analysis.
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瑞戈非尼加特瑞普利单抗治疗转移性结直肠癌患者：Ib/II 期临床试验和肠道微生物组分析
DOI：
10.1016/j.xcrm.2021.100383
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发表时间：
2021-09-21
期刊：
影响因子：
--
通讯作者：
Xu RH
中科院分区：
文献类型：
--
作者：
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
这是一项瑞格非尼联合托里普利单抗治疗结直肠癌的Ib/II期研究。采用推荐的II期剂量（80 mg瑞戈非尼加托里普利单抗）的可评估患者的客观缓解率（ORR）为15.2%，疾病控制率为36.4%。中位无进展生存期（PFS）和中位总生存期分别为2.1个月和15.5个月。肝转移患者的ORR低于无肝转移患者（8.7% vs 30.0%）。仅肺转移的所有患者（3/3）都有反应，而仅肝转移的患者无反应（0/4）。分别有94.9%和38.5%的患者发生1级和3级治疗相关不良事件。基线粪便样品的肠道微生物组分析显示，与应答者相比，无应答者中梭杆菌的相对丰度和阳性检出率显著增加。高丰度梭杆菌患者的PFS短于低丰度患者（中位PFS = 2.0 vs 5.2个月; p = 0.002）。Regorafenib + toripalimab改善了应答和总生存率。与应答者相比，在无应答者中发现了增加的梭杆菌。证明了瑞格非尼加托里普利单抗在结直肠癌患者中的安全性、有效性和存活率。他们显示了肠道微生物组的结果，即梭杆菌与反应和存活率呈负相关。这为难治性转移性结直肠癌患者提供了联合治疗方案。
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). Regorafenib plus toripalimab improves response and overall survival Patients with liver metastasis have lower response rate than those without Increased Fusobacterium is found in non-responders compared with responders Wang et al. demonstrate the safety, efficacy, and survival of regorafenib plus toripalimab in colorectal cancer patients. They show the gut microbiome results that Fusobacterium is negatively correlated with response and survival. This provides a combination regimen for unselected refractory metastatic colorectal cancer patients.
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