RECIST 和 iRECIST 标准用于评估纳武利尤单抗联合伊匹单抗治疗微卫星不稳定/错配修复缺陷转移性结直肠癌患者的疗效：GERCOR NIPICOL Ⅱ期研究。
RECIST and iRECIST criteria for the evaluation of nivolumab plus ipilimumab in patients with microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: the GERCOR NIPICOL phase II study.
机构信息
Sorbonne University, Department of Medical Oncology, Saint-Antoine Hospital, APHP, Paris, France.
Department of Medical Oncology, University Hospital of Nantes, Nantes, France.
出版信息
J Immunother Cancer. 2020 Nov;8(2). doi: 10.1136/jitc-2020-001499.
BACKGROUND
Immune checkpoint inhibitors (ICIs) are highly effective in patients with microsatellite instability/mismatch repair-deficient (MSI/dMMR) metastatic colorectal cancer (mCRC). Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria may underestimate response to ICIs due to the pseudoprogression phenomenon. The GERCOR NIPICOL phase II study aimed to evaluate the frequency of pseudoprogressions in patients with MSI/dMMR mCRC treated with nivolumab and ipilimumab.
METHODS
Patients with MSI/dMMR mCRC previously treated with fluoropyrimidines, oxaliplatin, and irinotecan with/without targeted therapies received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four cycles then nivolumab 3 mg/kg every 2 weeks until progression or a maximum of 20 cycles. Computed tomography scan tumor assessments were done every 6 weeks for 24 weeks and then every 12 weeks. The primary endpoint was disease control rate at 12 weeks according to RECIST 1.1 and iRECIST by central review.
RESULTS
Of 57 patients included between December 2017 and November 2018, 48.0% received ≥3 prior lines of chemotherapy, 18.0% had mutation, and 56.0% had Lynch syndrome-related cancer. Seven patients (12.0%) discontinued treatment due to adverse events; one died due to a treatment-related adverse event. The disease control rate (DCR) at 12 weeks was 86.0% with RECIST 1.1% and 87.7% with iRECIST. Two pseudoprogressions (3.5%) were observed, at week 6 and at week 36, representing 18% of patients with disease progression per RECIST 1.1 criteria. With a median follow-up of 18.4 months, median progression-free survival (PFS) and overall survival (OS) were not reached. The 12-month PFS rate was 72.9% with RECIST 1.1% and 76.5% with iRECIST. The 12-month OS rate was 84%. Overall response rate was 59.7% with both criteria. / status, sidedness, Lynch syndrome, and other baseline parameters were not associated with PFS.
CONCLUSION
Pseudoprogression is rare in patients with MSI/dMMR mCRC treated with nivolumab and ipilimumab. This combined ICI therapy confirms impressive DCR and survival outcomes in these patients.
TRIAL REGISTRATION NUMBER
NCT03350126.
背景
免疫检查点抑制剂（ICIs）在微卫星不稳定/错配修复缺陷（MSI/dMMR）转移性结直肠癌（mCRC）患者中具有高度疗效。由于假性进展现象，实体瘤反应评估标准 1.1（RECIST 1.1）可能低估了对 ICI 的反应。GERCOR NIPICOL 二期研究旨在评估接受纳武单抗和伊匹单抗治疗的 MSI/dMMR mCRC 患者中假性进展的频率。
方法
既往接受氟嘧啶、奥沙利铂和伊立替康联合/不联合靶向治疗的 MSI/dMMR mCRC 患者，每 3 周接受纳武单抗 3 mg/kg 联合伊匹单抗 1 mg/kg 治疗 4 个周期，然后每 2 周接受纳武单抗 3 mg/kg 治疗，直至疾病进展或最多 20 个周期。每 6 周进行一次计算机断层扫描肿瘤评估，共 24 周，然后每 12 周进行一次。主要终点是根据 RECIST 1.1 和中心评估的 iRECIST，在 12 周时的疾病控制率。
结果
2017 年 12 月至 2018 年 11 月期间，共纳入 57 例患者，其中 48.0%接受了≥3 线化疗，18.0%有 KRAS 突变，56.0%有 Lynch 综合征相关癌症。由于不良反应，有 7 例（12.0%）患者停止治疗；1 例患者因治疗相关不良反应死亡。12 周时，RECIST 1.1 为 86.0%，iRECIST 为 87.7%，疾病控制率（DCR）。观察到 2 例（3.5%）假性进展，分别在第 6 周和第 36 周，按 RECIST 1.1 标准，有 18%的患者疾病进展。中位随访 18.4 个月时，中位无进展生存期（PFS）和总生存期（OS）未达到。12 个月时，RECIST 1.1 为 72.9%，iRECIST 为 76.5%，PFS 率分别为 72.9%和 76.5%。12 个月 OS 率为 84%。两种标准的总缓解率均为 59.7%。/状态、侧别、Lynch 综合征和其他基线参数与 PFS 无关。
结论
纳武单抗和伊匹单抗治疗的 MSI/dMMR mCRC 患者中假性进展罕见。这种联合 ICI 治疗方案证实了这些患者具有令人印象深刻的 DCR 和生存获益。
试验注册
NCT03350126。
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