免疫检查点抑制剂治疗微卫星不稳定/错配修复缺陷转移性结直肠癌患者的假性进展。
Pseudoprogression in patients treated with immune checkpoint inhibitors for microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer.
机构信息
Sorbonne Université, Department of Medical Oncology, Saint-Antoine Hospital, AP-HP, 184 Rue Du Faubourg Saint-Antoine, 75012, Paris, France; Sorbonne University, Clinical Research Unit, Saint-Antoine Hospital, AP-HP, 184 Rue Du Faubourg Saint-Antoine, 75012, Paris, France.
Sorbonne University, Department of Radiology, Saint-Antoine Hospital, AP-HP, 184 Rue Du Faubourg Saint-Antoine, 75012, Paris, France.
出版信息
Eur J Cancer. 2021 Feb;144:9-16. doi: 10.1016/j.ejca.2020.11.009. Epub 2020 Dec 11.
BACKGROUND
The efficacy of immune checkpoint inhibitors (ICIs) in microsatellite instability-high/DNA mismatch repair (MSI/dMMR) metastatic colorectal cancer (mCRC) is well established. ICIs are responsible for pseudoprogression (PSPD) that complicates clinical decisions. We evaluated the PSPD frequency in patients with MSI/dMMR mCRC treated with ICIs.
PATIENTS AND METHODS
Consecutive patients with MSI/dMMR mCRC treated with ICIs from February 2015 to December 2019 at Saint-Antoine Hospital were included. Imaging was retrospectively and centrally reviewed according to Response Evaluation Criteria in Solid Tumours, version 1.1 (RECIST 1.1) and immune RECIST (iRECIST). PSPD was defined as an unconfirmed disease progression by iRECIST.
RESULTS
One hundred twenty-three patients with MSI/dMMR mCRC were included. Thirty-six patients (29%) had radiological PD according to RECIST 1.1 during the median follow-up of 22.3 months (95% confidence interval [CI], 1.5-62.2), including 22 in the first 3 months (the primary radiological PD). Twenty-nine patients continued ICIs beyond PD. Twelve patients experienced PSPD, representing 10% of the population and 52% of the primary radiological PD. The median time to PSPD was 5.7 weeks (95% CI, 4.1-11.4). No PSPD was observed after 3 months. The PSPD incidence was 14.8% in patients treated with anti-PD1 alone (n = 9/61) and 4.8% in case of anti-PD1 plus anti-CTLA-4 (n = 3/62). Eight patients with PSPD experienced an objective response. The 2-year progression-free survival and overall survival rates for patients with PSPD were 70.0% (95% CI, 32.9-89.2) and 75.0% (95% CI, 29.8-93.4), respectively.
CONCLUSION
Patients with MSI/dMMR mCRC treated with ICIs experienced PSPDs. PSPD occurred within the first 3 months and represented most of the primary radiological PDs. The use of iRECIST criteria should be questioned after 3 months.
背景
免疫检查点抑制剂（ICIs）在微卫星不稳定/DNA 错配修复（MSI/dMMR）转移性结直肠癌（mCRC）中的疗效已得到充分证实。ICI 可导致假性进展（PSPD），从而使临床决策变得复杂。我们评估了接受 ICI 治疗的 MSI/dMMR mCRC 患者的 PSPD 发生率。
患者和方法
连续纳入 2015 年 2 月至 2019 年 12 月期间在圣安东尼医院接受 ICI 治疗的 MSI/dMMR mCRC 患者。根据实体瘤反应评估标准，1.1 版（RECIST 1.1）和免疫 RECIST（iRECIST）对影像学进行回顾性和中心评估。PSPD 定义为 iRECIST 确认的疾病进展。
结果
共纳入 123 例 MSI/dMMR mCRC 患者。在中位随访 22.3 个月（95%置信区间 [CI]，1.5-62.2）期间，36 例（29%）患者根据 RECIST 1.1 出现影像学 PD，包括 3 个月内 22 例（原发性影像学 PD）。29 例患者在 PD 后继续接受 ICI 治疗。12 例患者发生 PSPD，占总人口的 10%，占原发性影像学 PD 的 52%。PSPD 的中位时间为 5.7 周（95%CI，4.1-11.4）。3 个月后未观察到 PSPD。单独使用抗 PD1 治疗的患者中 PSPD 的发生率为 14.8%（n=9/61），而联合使用抗 PD1 和抗 CTLA-4 的患者中 PSPD 的发生率为 4.8%（n=3/62）。8 例 PSPD 患者出现客观缓解。PSPD 患者的 2 年无进展生存率和总生存率分别为 70.0%（95%CI，32.9-89.2）和 75.0%（95%CI，29.8-93.4）。
结论
接受 ICI 治疗的 MSI/dMMR mCRC 患者发生 PSPD。PSPD 发生在 3 个月内，占大部分原发性影像学 PD。3 个月后应质疑 iRECIST 标准的应用。
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