仅有1项随机临床试验显示免疫检查点抑制剂在缺失错配修复和/或微卫星不稳定性（dMMR/MSI）转移性结直肠癌（mCRC）的一线治疗中具有优势。本研究旨在确定与标准二线化疗相比，阿维舒单抗（PD-L1抗体）是否能改善dMMR/MSI mCRC患者的无进展生存期（PFS）。SAMCO-PRODIGE 54试验是一项国家级开放标签的2期随机临床试验，于2018年4月24日至2021年4月29日期间在法国的49个研究中心进行。将分析所有在接受标准一线治疗期间出现疾病进展的dMMR/MSI mCRC患者。患者被随机分组接受标准二线治疗或每2周一次的阿维舒单抗治疗，直至疾病进展、无法接受的毒性效应或患者拒绝为止。主要终点是以RECIST（实体肿瘤疗效评估标准），版本1.1进行评估的PFS，由调查人员在接受至少1剂治疗的mCRC和确认的dMMR和MSI状态的患者中评估（修改的意向治疗[mITT]人群）。共有122名患者纳入mITT人群。中位年龄为66岁（IQR，56-76岁），65名患者（53.3%）为女性，100名患者（82.0%）为右侧肿瘤，52名患者（42.6%）为BRAF V600E突变肿瘤。治疗组间患者和肿瘤特征没有差异。在任何组别中都没有发现新的安全问题，阿维舒单抗组的至少3级治疗相关不良事件较化疗组较少（20例[31.7%] vs 34例[53.1%]; P = .02）。经过中位33.3（95% CI, 28.3-34.8）个月的随访后，与化疗治疗组相比，阿维舒单抗在PFS方面表现更佳（在未进展患者中，15例[24.6%] vs 5例[8.2%]; P = .03）。阿维舒单抗组和对照组分别为12个月PFS率为31.2% (95% CI，20.1%-42.9%)和19.4% (95% CI，10.6%-30.2%)，18个月PFS率为27.4% (95% CI，16.8%-39.0%)和9.1% (95% CI，3.2%-18.8%)。两组的客观缓解率相似（18例[29.5%] vs 16例[26.2%]; P = .45）。在疾病控制的患者中，阿维舒单抗组有18例（75.7%），而对照组有9例（19.1%）在18个月后仍持续疾病控制。SAMCO-PRODIGE 54第2期随机临床试验显示，在dMMR/MSI mCRC患者中，阿维舒单抗相较于标准二线治疗，表现出更好的PFS和疾病控制持续时间，并具有良好的安全性。ClinicalTrials.gov标识符：NCT03186326。

Only 1 randomized clinical trial has shown the superiority of immune checkpoint inhibitors in patients with deficient mismatch repair and/or microsatellite instability (dMMR/MSI) metastatic colorectal cancer (mCRC) in the first-line setting.To determine whether avelumab (an anti-programmed cell death ligand 1 antibody) improves progression-free survival (PFS) compared with standard second-line chemotherapy in patients with dMMR/MSI mCRC.The SAMCO-PRODIGE 54 trial is a national open-label phase 2 randomized clinical trial that was conducted from April 24, 2018, to April 29, 2021, at 49 French sites. Patients with dMMR/MSI mCRC who experienced progression while receiving standard first-line therapy were included in the analysis.Patients were randomized to receive standard second-line therapy or avelumab every 2 weeks until progression, unacceptable toxic effects, or patient refusal.The primary end point was PFS according to RECIST (Response Evaluation Criteria in Solid Tumours), version 1.1, evaluated by investigators in patients with mCRC and confirmed dMMR and MSI status who received at least 1 dose of treatment (modified intention-to-treat [mITT] population).A total of 122 patients were enrolled in the mITT population. Median age was 66 (IQR, 56-76) years, 65 patients (53.3%) were women, 100 (82.0%) had a right-sided tumor, and 52 (42.6%) had BRAF V600E-mutated tumors. There was no difference in patients and tumor characteristics between treatment groups. No new safety concerns in either group were detected, with fewer treatment-related adverse events of at least grade 3 in the avelumab group than in the chemotherapy group (20 [31.7%] vs 34 [53.1%]; P = .02). After a median follow-up of 33.3 (95% CI, 28.3-34.8) months, avelumab was superior to chemotherapy with or without targeted agents with respect to PFS (15 [24.6%] vs 5 [8.2%] among patients without progression; P = .03). Rates of PFS rates at 12 months were 31.2% (95% CI, 20.1%-42.9%) and 19.4% (95% CI, 10.6%-30.2%) in the avelumab and control groups, respectively, and 27.4% (95% CI, 16.8%-39.0%) and 9.1% (95% CI, 3.2%-18.8%) at 18 months. Objective response rates were similar in both groups (18 [29.5%] vs 16 [26.2%]; P = .45). Among patients with disease control, 18 (75.7%) in the avelumab group compared with 9 (19.1%) in the control group had ongoing disease control at 18 months.The SAMCO-PRODIGE 54 phase 2 randomized clinical trial showed, in patients with dMMR/MSI mCRC, better PFS and disease control duration with avelumab over standard second-line treatment, with a favorable safety profile.ClinicalTrials.gov Identifier: NCT03186326.