Abstract：
BACKGROUND: One randomized phase III trial comparing chemotherapy (CT) with immune checkpoint inhibitors (ICI) has demonstrated significant efficacy of ICI in deficient DNA mismatch repair system/microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer. However, few studies have compared ICI with CT in other advanced dMMR/MSI-H digestive tumors.
METHODS: In this multicenter study, we included patients with advanced dMMR/MSI-H non-colorectal digestive tumors treated with chemotherapy and/or ICIs. Patients were divided retrospectively into two groups, a CT group and an immunotherapy (IO) group. The primary endpoint was progression-free survival (PFS). A propensity score approach using the inverse probability of treatment weighting (IPTW) method was applied to deal with potential differences between the two groups.
RESULTS: 133 patients (45.1/27.1/27.8% with gastric/small bowel/other carcinomas) were included. The majority of patients received ICI in 1st (29.1%) or 2nd line (44.4%). The 24-month PFS rates were 7.9% in the CT group and 71.2% in the IO group. Using the IPTW method, IO treatment was associated with better PFS (HR=0.227; 95% CI 0.147-0.351; p < 0.0001). The overall response rate was 26.3% in the CT group versus 60.7% in the IO group (p < 0.001) with prolonged duration of disease control in the IO group (p < 0.001). In multivariable analysis, predictive factors of PFS for patients treated with IO were good performance status, absence of liver metastasis and prior primary tumor resection, whereas no association was found for the site of the primary tumor.
CONCLUSIONS: In the absence of randomized trials, our study highlights the superior efficacy of ICI compared with standard-of-care therapy in patients with unresectable or metastatic dMMR/MSI-H non-colorectal digestive cancer, regardless of tumor type, with acceptable toxicity.
METHODS: In this multicenter study, we included patients with advanced dMMR/MSI-H non-colorectal digestive tumors treated with chemotherapy and/or ICIs. Patients were divided retrospectively into two groups, a CT group and an immunotherapy (IO) group. The primary endpoint was progression-free survival (PFS). A propensity score approach using the inverse probability of treatment weighting (IPTW) method was applied to deal with potential differences between the two groups.
RESULTS: 133 patients (45.1/27.1/27.8% with gastric/small bowel/other carcinomas) were included. The majority of patients received ICI in 1st (29.1%) or 2nd line (44.4%). The 24-month PFS rates were 7.9% in the CT group and 71.2% in the IO group. Using the IPTW method, IO treatment was associated with better PFS (HR=0.227; 95% CI 0.147-0.351; p < 0.0001). The overall response rate was 26.3% in the CT group versus 60.7% in the IO group (p < 0.001) with prolonged duration of disease control in the IO group (p < 0.001). In multivariable analysis, predictive factors of PFS for patients treated with IO were good performance status, absence of liver metastasis and prior primary tumor resection, whereas no association was found for the site of the primary tumor.
CONCLUSIONS: In the absence of randomized trials, our study highlights the superior efficacy of ICI compared with standard-of-care therapy in patients with unresectable or metastatic dMMR/MSI-H non-colorectal digestive cancer, regardless of tumor type, with acceptable toxicity.
摘要：
背景：一项比较化疗（CT）与免疫检查点抑制剂（ICI）的随机III期试验已证明ICI在DNA错配修复系统缺陷/微卫星不稳定性高（dMMR/MSI-H）转移性结直肠癌中具有显著疗效。然而,很少有研究将ICI与CT在其他晚期dMMR/MSI-H消化道肿瘤中进行比较。
方法：在这项多中心研究中，我们纳入了接受化疗和/或ICIs治疗的晚期dMMR/MSI-H非结直肠消化道肿瘤患者.患者回顾性地分为两组,CT组和免疫治疗（IO）组。主要终点是无进展生存期（PFS）。使用治疗加权逆概率（IPTW）方法的倾向评分方法用于处理两组之间的潜在差异。
结果：纳入了133例患者（45.1/27.1/27.8％患有胃/小肠/其他癌）。大多数患者在第1行（29.1％）或第2行（44.4％）接受ICI。CT组和IO组24个月PFS分别为7.9%和71.2%。使用IPTW方法，IO治疗与更好的PFS相关(HR=0.227;95%CI0.147-0.351;p<0.0001)。CT组总有效率为26.3%，IO组为60.7%(p<0.001)，IO组疾病控制持续时间延长(p<0.001)。在多变量分析中，IO治疗患者PFS的预测因素是良好的表现状态，没有肝转移和先前的原发肿瘤切除，而原发肿瘤的部位没有发现相关性。
结论：在没有随机试验的情况下，我们的研究强调了ICI与标准治疗相比，在不可切除或转移性dMMR/MSI-H非结直肠消化性癌症患者中，ICI的疗效优于标准治疗，无论肿瘤类型，具有可接受的毒性。
方法：在这项多中心研究中，我们纳入了接受化疗和/或ICIs治疗的晚期dMMR/MSI-H非结直肠消化道肿瘤患者.患者回顾性地分为两组,CT组和免疫治疗（IO）组。主要终点是无进展生存期（PFS）。使用治疗加权逆概率（IPTW）方法的倾向评分方法用于处理两组之间的潜在差异。
结果：纳入了133例患者（45.1/27.1/27.8％患有胃/小肠/其他癌）。大多数患者在第1行（29.1％）或第2行（44.4％）接受ICI。CT组和IO组24个月PFS分别为7.9%和71.2%。使用IPTW方法，IO治疗与更好的PFS相关(HR=0.227;95%CI0.147-0.351;p<0.0001)。CT组总有效率为26.3%，IO组为60.7%(p<0.001)，IO组疾病控制持续时间延长(p<0.001)。在多变量分析中，IO治疗患者PFS的预测因素是良好的表现状态，没有肝转移和先前的原发肿瘤切除，而原发肿瘤的部位没有发现相关性。
结论：在没有随机试验的情况下，我们的研究强调了ICI与标准治疗相比，在不可切除或转移性dMMR/MSI-H非结直肠消化性癌症患者中，ICI的疗效优于标准治疗，无论肿瘤类型，具有可接受的毒性。
