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Detection of microsatellite instability-high (MSI-H) by liquid biopsy predicts robust and durable response to immunotherapy in patients with pancreatic cancer

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 bi...

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Autores principales: Chakrabarti, Sakti, Bucheit, Leslie, Starr, Jason Scott, Innis-Shelton, Racquel, Shergill, Ardaman, Dada, Hiba, Resta, Regina, Wagner, Stephanie, Fei, Naomi, Kasi, Pashtoon Murtaza
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10098262/
https://www.ncbi.nlm.nih.gov/pubmed/35710297
http://dx.doi.org/10.1136/jitc-2021-004485
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author Chakrabarti, Sakti
Bucheit, Leslie
Starr, Jason Scott
Innis-Shelton, Racquel
Shergill, Ardaman
Dada, Hiba
Resta, Regina
Wagner, Stephanie
Fei, Naomi
Kasi, Pashtoon Murtaza
author_facet Chakrabarti, Sakti
Bucheit, Leslie
Starr, Jason Scott
Innis-Shelton, Racquel
Shergill, Ardaman
Dada, Hiba
Resta, Regina
Wagner, Stephanie
Fei, Naomi
Kasi, Pashtoon Murtaza
author_sort Chakrabarti, Sakti
collection PubMed
description 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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spelling pubmed-100982622023-04-14 Detection of microsatellite instability-high (MSI-H) by liquid biopsy predicts robust and durable response to immunotherapy in patients with pancreatic cancer Chakrabarti, Sakti Bucheit, Leslie Starr, Jason Scott Innis-Shelton, Racquel Shergill, Ardaman Dada, Hiba Resta, Regina Wagner, Stephanie Fei, Naomi Kasi, Pashtoon Murtaza J Immunother Cancer Immunotherapy Biomarkers 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. BMJ Publishing Group 2022-06-16 /pmc/articles/PMC10098262/ /pubmed/35710297 http://dx.doi.org/10.1136/jitc-2021-004485 Text en © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Immunotherapy Biomarkers
Chakrabarti, Sakti
Bucheit, Leslie
Starr, Jason Scott
Innis-Shelton, Racquel
Shergill, Ardaman
Dada, Hiba
Resta, Regina
Wagner, Stephanie
Fei, Naomi
Kasi, Pashtoon Murtaza
Detection of microsatellite instability-high (MSI-H) by liquid biopsy predicts robust and durable response to immunotherapy in patients with pancreatic cancer
title Detection of microsatellite instability-high (MSI-H) by liquid biopsy predicts robust and durable response to immunotherapy in patients with pancreatic cancer
title_full Detection of microsatellite instability-high (MSI-H) by liquid biopsy predicts robust and durable response to immunotherapy in patients with pancreatic cancer
title_fullStr Detection of microsatellite instability-high (MSI-H) by liquid biopsy predicts robust and durable response to immunotherapy in patients with pancreatic cancer
title_full_unstemmed Detection of microsatellite instability-high (MSI-H) by liquid biopsy predicts robust and durable response to immunotherapy in patients with pancreatic cancer
title_short Detection of microsatellite instability-high (MSI-H) by liquid biopsy predicts robust and durable response to immunotherapy in patients with pancreatic cancer
title_sort detection of microsatellite instability-high (msi-h) by liquid biopsy predicts robust and durable response to immunotherapy in patients with pancreatic cancer
topic Immunotherapy Biomarkers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10098262/
https://www.ncbi.nlm.nih.gov/pubmed/35710297
http://dx.doi.org/10.1136/jitc-2021-004485
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