Pan-Cancer Prevalence of Microsatellite Instability-High (MSI-H) Identified by Circulating Tumor DNA and Associated Real-World Clinical Outcomes.
Academic Article
Overview
abstract
PURPOSE: Immune checkpoint inhibitors are approved for advanced solid tumors with microsatellite instability-high (MSI-H). Although several technologies can assess MSI-H status, detection and outcomes with circulating tumor DNA (ctDNA)-detected MSI-H are lacking. As such, we examined pan-cancer MSI-H prevalence across 21 cancers and outcomes after ctDNA-detected MSI-H. METHODS: Patients with advanced cancer who had ctDNA testing (Guardant360) from October 1, 2018, to June 30, 2022, were retrospectively assessed for prevalence. GuardantINFORM, which includes anonymized genomic and structured payer claims data, was queried to assess outcomes. Patients who initiated new treatment within 90 days of MSI-H detection were sorted into immunotherapy included in treatment (IO) or no immunotherapy included (non-IO) groups. Real-world time to treatment discontinuation (rwTTD) and real-world time to next treatment (rwTTNT) were assessed in months as proxies of progression-free survival (PFS); real-world overall survival (rwOS) was assessed in months. Cox regression tests analyzed differences. Colorectal cancer, non-small-cell lung cancer (NSCLC), prostate cancer, gastroesophageal cancer, and uterine cancer (UC) were assessed independently; all other cancers were grouped. RESULTS: In total, 1.4% of 171,881 patients had MSI-H detected. Of 770 patients with outcomes available, rwTTD and rwTTNT were significantly longer for patients who received IO compared with non-IO for all cancers (P ≤ .05; hazard ratio [HR] range, 0.31-0.52 and 0.25-0.54, respectively) except NSCLC. rwOS had limited follow-up for all cohorts except UC (IO 39 v non-IO 23 months; HR, 0.18; P = .004); however, there was a consistent trend toward prolonged OS in IO-treated patients. CONCLUSION: These data support use of a well-validated ctDNA assay to detect MSI-H across solid tumors and suggest prolonged PFS in patients treated with IO-containing regimens after detection. Tumor-agnostic, ctDNA-based MSI testing may be reliable for rapid decision making.
