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. 2025 Mar 3;8(3):e251186.
doi: 10.1001/jamanetworkopen.2025.1186.

Practice Patterns and Survival Outcomes of Immunotherapy for Metastatic Colorectal Cancer

Shahla Bari  1 , Marco Matejcic  2 , Richard D Kim  3 , Hao Xie  4 , Ibrahim H Sahin  5 , Benjamin D Powers  6   7 , Jamie K Teer  2 , Timothy A Chan  8 , Seth I Felder  3 , Stephanie L Schmit  9   10
Affiliations

Practice Patterns and Survival Outcomes of Immunotherapy for Metastatic Colorectal Cancer

Shahla Bari et al. JAMA Netw Open. .

Abstract

Importance: 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.

Objective: To identify factors associated with receipt of ICIs and associated survival outcomes among patients with mCRC in routine clinical practice.

Design, setting, and participants: 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.

Exposure: Patients received ICI therapy and/or chemotherapy as part of a systemic treatment for mCRC.

Main outcomes and measures: The outcomes were receipt of ICI therapy, overall survival (OS), and time to treatment discontinuation (TTD).

Results: 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.

Conclusions and relevance: 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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Chan reported being a cofounder of Gritstone Oncology and holds equity; grant funding from Bristol-Myers Squibb, AstraZeneca, Illumina, Pfizer, An2H, and Eisai; served as an advisor for Bristol-Myers, MedImmune, Squibb, Illumina, Eisai, AstraZeneca, and An2H; and is an inventor on intellectual property held by Memorial Sloan Kettering Cancer Center on using tumor mutation burden to predict immunotherapy response, with pending patent, which has been licensed to PGDx. Dr Felder reports a role on the advisory board of GSK and research funding from Natera and ViewRay. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Kaplan-Meier Survival Curves for Overall Survival (OS) and Time to Treatment Discontinuation (TTD) in All Patients With Metastatic Colorectal Cancer
Index date was the first episode of any systemic treatment regimen administered on or after the date of metastatic disease being diagnosed. For patients who died during the study period (n = 10 783), the correlation between OS and TTD was estimated using the Spearman rank test: ρ = 0.63 (95% CI, 0.61-0.64).
Figure 2.
Figure 2.. Kaplan-Meier Curves for Overall Survival (OS) and Time to Treatment Discontinuation (TTD) by Microsatellite Stability Status Among Patients With Metastatic Colorectal Cancer Treated With Immunotherapy
Index date was the start of immune checkpoint inhibitor (ICI)-based therapy defined as the first administration or noncancelled order of any of the following drugs: nivolumab, pembrolizumab, atezolizumab, ipilimumab, tremelimumab, durvalumab, or avelumab. A, Patients with microsatellite instable (MSI-H) tumors had a significantly reduced hazard of death (overall survival log-rank P < .001) compared with patients with microsatellite stable (MSS) tumors. B, Patients with MSI-H tumors had a significantly lower likelihood of immunotherapy discontinuation (TTD log-rank P < .001) relative to patients with MSS tumors.
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References

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