Clinical and Molecular Variables Associated With Early Progression to Checkpoint Inhibitors in MSI-High Metastatic Colorectal Cancer: A Retrospective Cohort Study
L. Hulst, S. Cappuyns, F. Peeters, F. Vulsteke, F. Van Herpe, E. Van Cutsem, J. Dekervel
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Abstract
Background
About one third of patients with deficient mismatch repair/microsatellite instability-high metastatic colorectal cancer (dMMR/MSI-H mCRC) experience primary resistance or early progression on immune checkpoint inhibitors (ICI), while others benefit from exceptionally long-lasting responses. In this single-centre retrospective study, we aimed to identify variables associated with improved overall survival (OS) as well as early disease progression.
Methods
All dMMR/MSI-H mCRC patients treated with ICI between 2014 and 2022 were included. Baseline patient demographics, tumour characteristics as well response and outcome data were recorded. OS was estimated using the Kaplan–Meier method. Uni- and multivariate cox regression analysis was used to identify parameters associated with improved OS. Clinicopathological factors associated with early progression (≤ 12 months after treatment initiation) were assessed using uni- and multivariate logistic regression analysis.
Results
About 84 ICI-treated dMMR/MSI-H mCRC patients were included. Progressive disease occurred in 37 (44%) patients, but only in 11 (19%) patients with disease control at 12 months. Median OS was 80 months and improved outcome was associated with a lower neutrophile-to-lymphocyte ratio (NLR) (P = .004) and the presence of immune-related adverse events (irAEs) (P = .015). Early progression was associated with poor performance status (P = .036), a higher blood CRP level (P = .033) and absence of irAEs (P = .002).
Conclusion
Disease progression in ICI-treated dMMR/MSI-H mCRC rarely occurs in patients experiencing disease control for at least 12 months. Performance status, presence of immune-related adverse events, CRP levels, CEA levels and NLR can be helpful to identify those patients that may benefit from ICI treatment, guiding clinicians in therapeutic decisions.
期刊介绍：
Clinical Colorectal Cancer is a peer-reviewed, quarterly journal that publishes original articles describing various aspects of clinical and translational research of gastrointestinal cancers. Clinical Colorectal Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of colorectal, pancreatic, liver, and other gastrointestinal cancers. The main emphasis is on recent scientific developments in all areas related to gastrointestinal cancers. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.
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