Assistance Publique - Hôpitaux de Paris, European Georges Pompidou hospital, Department of oncology, Paris France; Centre de Recherche des Cordeliers, INSERM, CNRS, Sorbonne Université, USPC, Université de Paris, Equipe labellisée Ligue Nationale contre le cancer, Paris, France.
Sorbonne Université and Hôpital Saint Antoine, Paris, France.
Dig Liver Dis. 2021 Mar;53(3):318-323. doi: 10.1016/j.dld.2020.11.031. Epub 2020 Dec 25.
Immune checkpoint inhibitors have failed in treating metastatic colorectal cancer (mCRC) patients except those with dMMR/MSI tumors. However, until very recently we had only non-comparative promising data in this population with anti-programmed cell death 1/ programmed cell death ligand 1 (PD1/PD-L1) antibodies alone or combined with anti- cytotoxic T-lymphocyte-associated protein 4 (CTLA4) antibodies. This comparative phase II trial (NCT03186326), conducted in more than 100 centers in France, will include dMMR/MSI mCRC patients with progression after a first-line treatment with chemotherapy ± targeted therapies, to evaluate efficacy and safety of the anti-PDL1 Avelumab versus a standard second-line treatment. Main inclusion criteria were patients aged 18 to 75 years, ECOG performance status ≤2, dMMR/MSI mCRC and failure of a standard first-line regimen. Patient will be randomised to receive Avelumab 10 mg/kg versus standard second-line doublet chemotherapy plus a targeted agent according to tumor RAS status. Patients will be followed for 4 years. A gain of 5 months in median PFS is expected in favour of the Avelumab arm (12 vs 7 months; HR=0.58). Secondary endpoints include objective response rate, overall survival, quality of life and toxicity. In addition, circulating tumour DNA and microbiota will be explored to test their potential prognostic and predictive values. The study was opened in March 2018.
免疫检查点抑制剂在治疗转移性结直肠癌（mCRC）患者方面已经失败，除了那些具有错配修复缺陷/微卫星不稳定（dMMR/MSI）肿瘤的患者。然而，直到最近，我们在这一人群中只有非对照的、有前景的数据，使用抗程序性细胞死亡 1/程序性细胞死亡配体 1（PD1/PD-L1）抗体单独或联合抗细胞毒性 T 淋巴细胞相关蛋白 4（CTLA4）抗体。这项在法国 100 多个中心进行的比较性 II 期试验（NCT03186326），将包括在一线化疗±靶向治疗后进展的 dMMR/MSI mCRC 患者，以评估抗 PD-L1 药物 Avelumab 与标准二线治疗相比的疗效和安全性。主要纳入标准为年龄在 18 至 75 岁之间、ECOG 表现状态≤2、dMMR/MSI mCRC 和标准一线方案失败的患者。患者将被随机分配接受 Avelumab 10mg/kg 或标准二线双联化疗加靶向药物，根据肿瘤 RAS 状态。患者将随访 4 年。预计 Avelumab 组的中位无进展生存期（PFS）将延长 5 个月（12 个月 vs 7 个月；HR=0.58）。次要终点包括客观缓解率、总生存期、生活质量和毒性。此外，还将探索循环肿瘤 DNA 和微生物组，以测试它们的潜在预后和预测价值。该研究于 2018 年 3 月开始。
