@article {Chakrabartie004485, author = {Sakti Chakrabarti and Leslie Bucheit and Jason Scott Starr and Racquel Innis-Shelton and Ardaman Shergill and Hiba Dada and Regina Resta and Stephanie Wagner and Naomi Fei and Pashtoon Murtaza Kasi}, title = {Detection of microsatellite instability-high (MSI-H) by liquid biopsy predicts robust and durable response to immunotherapy in patients with pancreatic cancer}, volume = {10}, number = {6}, elocation-id = {e004485}, year = {2022}, doi = {10.1136/jitc-2021-004485}, publisher = {BMJ Specialist Journals}, abstract = {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{\textendash}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{\textendash}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{\textendash}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.No data are available. Not applicable.}, URL = {https://jitc.bmj.com/content/10/6/e004485}, eprint = {https://jitc.bmj.com/content/10/6/e004485.full.pdf}, journal = {Journal for ImmunoTherapy of Cancer} }