Detection of microsatellite instability-high (MSI-H) by liquid biopsy predicts robust and durable response to immunotherapy in patients with pancreatic cancer.
Detection of microsatellite instability-high (MSI-H) by liquid biopsy predicts robust and durable response to immunotherapy in patients with pancreatic cancer.
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DOI：
10.1136/jitc-2021-004485
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发表时间：
2022-06
影响因子：
10.9
通讯作者：
Kasi, Pashtoon Murtaza
中科院分区：
文献类型：
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作者：
Chakrabarti, Sakti;Bucheit, Leslie;Starr, Jason Scott;Innis-Shelton, Racquel;Shergill, Ardaman;Dada, Hiba;Resta, Regina;Wagner, Stephanie;Fei, Naomi;Kasi, Pashtoon Murtaza
报告免疫检查点抑制剂（ICI）在微卫星不稳定性高（MSI-H）实体瘤中具有强大抗肿瘤活性的临床试验使用基于组织的测试来确定MSI-H状态。本研究评估了在胰腺导管腺癌（PDAC）患者中，通过基于血浆的循环肿瘤DNA液体活检试验检测到的MSI-H是否可预测ICI的稳健应答。对2018年10月至2021年4月期间在Guardant 360上发现的PDAC和MSI-H患者进行了回顾性分析;治疗提供者提交了临床结局。在52例PDAC +MSI-H患者中，10例（19%）结局可用，中位年龄为68岁（范围：56-82岁）;大多数为男性（80%）和转移性疾病（80%）。10例患者中有9例接受了ICI治疗。九名患者中有八名接受了单药派姆单抗（8/9），而一名接受了伊匹单抗加纳武单抗。根据实体瘤疗效评价标准，总有效率为77%（7/9）。该队列未达到中位无进展生存期和总生存期。ICI治疗的中位持续时间为8个月（范围：1-24），在中位随访21个月（范围：11-33）后，7例应答者中有6例在数据截止时继续显示应答。基于组织的MSI结果与基于血浆的G360结果一致，其中6例患者中有5例（83%）具有基于组织的测试结果，G360比组织测试多识别一名MSI-H患者。这些结果表明，通过经过充分验证的液体活检检测MSI-H可以预测PDAC患者对ICI的稳健反应。液体活检的使用可以扩大对患有MSI-H肿瘤的PDAC患者的识别，并使ICI治疗能够改善结局。
Clinical trials reporting the robust antitumor activity of immune checkpoint inhibitors (ICIs) in microsatellite instability-high (MSI-H) solid tumors have used tissue-based testing to determine the MSI-H status. This study assessed if MSI-H detected by a plasma-based circulating tumor DNA liquid biopsy test predicts robust response to ICI in patients with pancreatic ductal adenocarcinoma (PDAC). Retrospective analysis of patients with PDAC and MSI-H identified on Guardant360 from October 2018 to April 2021 was performed; clinical outcomes were submitted by treating providers. From 52 patients with PDAC +MSI-H, outcomes were available for 10 (19%) with a median age of 68 years (range: 56–82 years); the majority were male (80%) and had metastatic disease (80%). Nine of 10 patients were treated with ICI. Eight out of nine patients received single-agent pembrolizumab (8/9), while one received ipilimumab plus nivolumab. The overall response rate by Response Evaluation Criteria in Solid Tumors was 77% (7/9). The median progression-free survival and overall survival were not reached in this cohort. The median duration of treatment with ICI was 8 months (range: 1–24), and six out of seven responders continued to show response at the time of data cut-off after a median follow-up of 21 months (range: 11–33). Tissue-based MSI results were concordant with plasma-based G360 results in five of six patients (83%) who had tissue-based test results available, with G360 identifying one more patient with MSI-H than tissue testing. These results suggest that detecting MSI-H by a well-validated liquid biopsy test could predict a robust response to ICI in patients with PDAC. The use of liquid biopsy may expand the identification of PDAC patients with MSI-H tumors and enable treatment with ICI resulting in improved outcomes.
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DOI：
10.1158/1078-0432.ccr-17-3099
发表时间：
2018-03-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Hu ZI;Shia J;Stadler ZK;Varghese AM;Capanu M;Salo-Mullen E;Lowery MA;Diaz LA Jr;Mandelker D;Yu KH;Zervoudakis A;Kelsen DP;Iacobuzio-Donahue CA;Klimstra DS;Saltz LB;Sahin IH;O'Reilly EM
通讯作者：
O'Reilly EM
影响因子：
45.3
作者：
Overman, Michael J.;Lonardi, Sara;Andre, Thierry
通讯作者：
Andre, Thierry
影响因子：
2.9
作者：
Larson, Brent K.;Tuli, Richard;Hendifar, Andrew E.
通讯作者：
Hendifar, Andrew E.
DOI：
10.7759/cureus.14640
发表时间：
2021-04-22
期刊：
Cureus
影响因子：
--
作者：
Cox RE Jr;Mahipal A;Chakrabarti S
通讯作者：
Chakrabarti S
影响因子：
11.5
作者：
Willis, Jason;Lefterova, Martina I.;Odegaard, Justin I.
通讯作者：
Odegaard, Justin I.