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

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

A. Hollebecque: Financial Interests, Personal, Invited Speaker: Servier, Incyte, Eisai; Financial Interests, Personal, Advisory Board: Basilea, Tahio, Relay Theraeutics, QED Therapeutics, Debiopharm, MSD, Boehringer Ingelheim; Financial Interests, Institutional, Funding: Incyte; Financial Interests, Institutional, Research Grant: AstraZeneca; Non-Financial Interests, Principal Investigator, M19-345: AbbVie; Non-Financial Interests, Principal Investigator, CO42216; WP42627; CO40939: Roche; Non-Financial Interests, Principal Investigator, MCLA-158: Merus; Non-Financial Interests, Principal Investigator, SGNB6A: Seatle Genetics; Non-Financial Interests, Principal Investigator, TAS-120-202: Tahio; Non-Financial Interests, Principal Investigator, Krystal-10: Mirati; Non-Financial Interests, Principal Investigator, ADP-0033: Adaptimmune; Non-Financial Interests, Principal Investigator, ACT16902: Sanofi; Non-Financial Interests, Principal Investigator, C4201002: Pfizer; Non-Financial Interests, Principal Investigator, RLY-4008: Relay Therapeutics; Non-Financial Interests, Principal Investigator, CC-90011: Celgene/BMS; Non-Financial Interests, Principal Investigator, Loxo-IDH: Loxo/Lilly; Non-Financial Interests, Principal Investigator: AstraZeneca; Non-Financial Interests, Principal Investigator, SN-201 study: Sotio; Non-Financial Interests, Principal Investigator, Tropics-03: Gilead; Non-Financial Interests, Principal Investigator, BI1403: Boehringer Ingelheim. A. Italiano: Financial Interests, Personal, Advisory Board: Bayer, Roche, Philips, Chugai, GSK; Financial Interests, Institutional, Coordinating PI: Bayer, AstraZeneca, Roche, MSD, Ipsen, Merck. All other authors have declared no conflicts of interest.