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

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: 56–82 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.

Development and validation of a deacetylation regulators-related prognostic signature in gastric cancer

“…TMB and MSI could also affect patients' response of immunotherapy in a variety of cancers. Patients with a higher TMB level and MSI-H might be more sensitive to immunotherapy [39,40]. In our result, we found a negative correlation between risk score and TMB level/MSI-H. Taken all these evidences into consideration, our risk signature could be utilized to predict immunotherapy response of GC patients.…”

The potential clinical utility of cell-free DNA for gastric cancer patients treated with nivolumab monotherapy

“…Regarding molecular features on liquid biopsy, one of our important ndings was that plasma-based MSI-H and tissue-based dMMR status were in 100% concordance. As shown in previous studies 16, 29 , MSI-H determination by liquid biopsy may provide a convenient approach for determining ICI eligibility for gastric cancer patients. On the other hand, we did not observe any single genetic alteration that was associated with a therapeutic effect of nivolumab.…”

The potential clinical utility of cell-free DNA for gastric cancer patients treated with nivolumab monotherapy

“…Regarding molecular features on liquid biopsy, one of our important findings was that plasma-based MSI-H and tissue-based dMMR status were in 100% concordance. As shown in previous studies 16,25 , MSI-H determination by liquid biopsy may provide a convenient approach for determining ICI eligibility for gastric cancer patients. On the other hand, we did not observe any single genetic alteration that was associated with a therapeutic effect of nivolumab.…”