143P Is liquid biopsy a good tool for microsatellite instability (MSI) assessment in solid tumors?

J.E. Rodriguez, K. Beshiri, D. Vasseur, A. Bayle, P. Cascetta, A. Patrikidou,M.V. Sanchez Becerra, M. Tagliamento, M. Aldea, L. Zullo, J.T.M.L. Ribeiro, M. Sakkal, K. Ouali, C. Parisi, A. Hollebecque, O. Cabaret, E. Rouleau, L. Lacroix, A. Italiano, C. Smolenschi

Annals of Oncology(2023)

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摘要
Within the last decade, immunotherapy revolutionized cancer treatment and patients (pts) prognosis. MSI is a validated biomarker of response to immune checkpoint blockers (ICB). In daily practice, Immunohistochemistry (IHC) and polymerase chain reaction (PCR) are the most recommended techniques for MSI detection. Lately, next generation sequencing (NGS) performed on liquid biopsy emerged as a new tool for MSI detection and can be used as an alternative to IHC/PCR analysis on tissue. We aim to describe the characteristics of a cohort of pts with MSI solid tumors detected by liquid biopsy and to evaluate the concordance with IHC and NGS testing. Data was collected from medical records and molecular profile reports (Foundation One Liquid CDx Assay – 324 genes) performed within the STING trial (NCT04932525) between June 2021 and April 2023. Among 4535 pts who underwent liquid biopsies, we found 1.5% (n=70 ) pts with a MSI positive status. The main characteristics were: 51% (n=36) were male with a median age of 68 years [32-89]. 24% of pts (n=17) had a known Lynch Syndrome. Most common tumor locations were colorectal (23%) and endometrial (16%). Median tumor fraction was 26% [10%-73%] and median tumor mutational burden (TMB) 113 mut/Mb [4-1450]. 40% (n=28) of pts had MSI positive tumor assessed by IHC and 55% (n=39) by NGS, with a concordance of 41%. A proportion of 58% (n=41) received ICB for advanced disease; pembrolizumab was the most frequent ICB administered and 66% (n=27) had received a median of 3 [1-8] prior lines of cytotoxic drugs. Median progression free survival (PFS) for concordant MSI status was 25 months (m) vs 9 m for non-concordant MSI (p=0.03), respectively. MSI concordance on liquid biopsy with MSI on tumor were considerably lower than reported in the literature. However, PFS was better in pts with a concordant status than those with either MSI/IHC or MSI/NGS alone or in tissue.
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关键词
liquid biopsy,microsatellite instability,solid tumors,msi
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