Clinical utility of microsatellite instability (MSI-H) identified on liquid biopsy in advanced gastrointestinal cancers (aGI).

Abstract

56 Background: Identification of MSI-H is clinically meaningful in patients with aGI given the associated approval of multiple immune checkpoint inhibitors. MSI-H has long been assessed via tissue analysis; and insights from plasma-based approaches are limited to small validation studies. We sought to assess prevalence of initial and acquired MSI-H status across aGI and report real-world outcomes of colorectal (CRC) patients who received ICI after MSI-H identification by a commercially available liquid biopsy (LBx) assay. Methods: Genomic results from a well-validated LBx assay (Guardant360) completed as part of usual clinical care between 10/1/2018-9/7/2021 in patients with aGI were queried to assess MSI-H prevalence and identify cases of potential acquired MSI-H. Real-world evidence (RWE) was sourced from the GuardantINFORM database comprised of aggregated payer claims and de-identified records from 11/1/2018-3/31/2021. Patients with plasma-identified MSI-H who started new therapy < 60 days after assay report date were sorted into treatment groups: chemotherapy +/- biologic therapy (“chemo”) or immunotherapy via pembrolizumab or nivolumab (“ICI”). Real-world time to discontinuation (rwTTD) and real-world time to next treatment (rwTTNT) were assessed as proxies for progression free survival. Log-rank tests were used to assess differences in rwTTD, rwTTNT and overall survival. Results: Prevalence of MSI-H was ̃2% across aGI (Table). Five cases were observed to have potential acquired MSI not attributable to tumor shed identified on serial LBx tests. Of 222 MSI-H CRC patients eligible for RWE analysis, 89(40%) started new therapy within 60 days of results: 42(48%) received ICI, 39(44%) received chemo, 8(9%) received other/mixed regimens. Patients who received ICI had significantly longer rwTTD and rwTTNT compared to patients who received chemo [median months to discontinuation = 7.5 (95% CI 3.4-12.3) vs. 2 (95% 1.4-3.3) p<0.001; median months to next treatment = 23.8 (95% 10.6-NA) vs. 4.5 (95% CI 2.9-NA) p=0.006]; no overall survival difference was observed (p=0.559). Conclusions: This LBx assay detected MSI-H at similar frequencies to published tissue cohorts and may identify acquired MSI-H following early lines of therapy. Patients who received ICI following LBx identification of MSI-H achieved responses in line with published data in previously treated aGI. Well-validated LBx is a viable tool to identify initial and acquired MSI-H in aGI and may expand the number of patients who could benefit from ICI therapy, particularly in cases where access to tissue specimens is not feasible. [Table: see text]