Practice Patterns and Survival Outcomes of Immunotherapy for Metastatic Colorectal Cancer

• Published in: JAMA network open Vol. 8; no. 3; p. e251186
• Main Authors: Bari, Shahla, Matejcic, Marco, Kim, Richard D., Xie, Hao, Sahin, Ibrahim H., Powers, Benjamin D., Teer, Jamie K., Chan, Timothy A., Felder, Seth I., Schmit, Stephanie L.
• Format: Journal Article
• Language: English
• Published: United States American Medical Association 03.03.2025
• Subjects: Aged; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; Electronic Health Records - statistics & numerical data; Female; Humans; Immune Checkpoint Inhibitors - therapeutic use; Immunology; Immunotherapy - methods; Immunotherapy - statistics & numerical data; Kaplan-Meier Estimate; Male; Microsatellite Instability; Middle Aged; Neoplasms, Multiple Primary - drug therapy; Neoplasms, Multiple Primary - genetics; Neoplasms, Multiple Primary - mortality; Neoplasms, Multiple Primary - pathology; Online Only; Original Investigation; Practice Patterns, Physicians' - statistics & numerical data; Retrospective Studies; Time Factors; Treatment Outcome
• ISSN: 2574-3805; 2574-3805
• DOI: 10.1001/jamanetworkopen.2025.1186

Immune checkpoint inhibitors (ICIs) have been approved for treatment of microsatellite instable (MSI-H) metastatic colorectal cancer (mCRC), but factors associated with receipt and efficacy of ICIs in routine clinical practice remain largely unknown. To identify factors associated with receipt of ICIs and associated survival outcomes among patients with mCRC in routine clinical practice. This population-based cohort study used deidentified data from a nationwide electronic health record-derived database to include 18 932 patients diagnosed with mCRC between January 2013 and June 2019. Population-based patients were diagnosed with de novo mCRC and had at least 2 documented clinical visits on or after the date of diagnosis. The study analyses were performed between September 2020 and April 2021. Patients received ICI therapy and/or chemotherapy as part of a systemic treatment for mCRC. The outcomes were receipt of ICI therapy, overall survival (OS), and time to treatment discontinuation (TTD). In this cohort study of 18 932 patients diagnosed with mCRC (10 537 [55.7%] male; 546 [2.9%] Asian, 2005 [10.6%] Black or African American, 1674 [8.8%] Hispanic, 12 338 [65.2%] White, 4043 [21.4%] unknown race or ethnicity; median [IQR] age at metastatic diagnosis, 64.6 [55.0-73.3] years), patients with MSI-H tumors had a significantly higher probability of receiving ICIs than those with microsatellite stable (MSS) tumors (odds ratio [OR], 22.66 [95% CI, 17.30-29.73]; P < .001), whereas patients initially diagnosed with synchronous mCRC had significantly lower odds of receiving ICIs than patients with metachronous mCRC (OR, 0.57 [95% CI, 0.45-0.73]; P < .001). Patients with MSI-H tumors who received ICIs as first line of therapy had significantly longer OS than those receiving chemotherapy only (HR, 0.37 [95% CI, 0.25-0.56]; P < .001). Among patients with MSS tumors, ICI-based therapy was associated with significantly longer OS for patients with high albumin level (vs low: HR, 0.28 [95% CI, 0.18-0.45]; P < .001) and antibiotic use (vs nonuse: HR, 0.43 [95% CI, 0.27-0.67]; P < .001), but a significantly shorter OS for patients with synchronous mCRC (vs metachronous: HR, 1.90 [95% CI, 1.24-2.89]; P = .003). In addition, 29 out of 235 patients with MSS tumors (12.3%) experienced durable responses on ICI-based therapy. Similar patterns of associations with TTD were observed. In this cohort study of patients with mCRC, clinical characteristics were associated with different survival outcomes in patients treated with ICI-based therapy, with important clinical implications for patients with MSS tumors who are generally unresponsive to immunotherapy.