In a U.S. population–based cohort study reported in JAMA Network Open, Bari et al identified patterns of immune checkpoint inhibitor (ICI) use and survival outcomes among patients with metastatic colorectal cancer seen in routine clinical practice.
The investigators stated: “…ICIs have been approved for treatment of microsatellite instable (MSI-H) metastatic colorectal cancer…, but factors associated with receipt and efficacy of ICIs in routine clinical practice remain largely unknown.”
Study Details
The study used the nationwide Flatiron Health electronic health record–derived deidentified database to collect data on 18,932 patients diagnosed between January 2013 and June 2019. Eligible patients were diagnosed with de novo metastatic disease and had at least two documented clinical visits on or after the date of diagnosis.
Key Findings
Among the 18,932 patients, 55.7% were male, 2.9% were Asian, 10.6% were Black/African American, 8.8% were Hispanic, 65.2% were White, and 21.4% were of unknown race/ethnicity. Median patient age at metastatic diagnosis was 64.6 years (interquartile range = 55.0–73.3 years).
Among the 18,932 patients, 566 (3.0%) received ICIs at some point during treatment. Among the 6,451 patients (34.1%) diagnosed with metastatic colorectal cancer after U.S. Food and Drug Administration approval of ICIs for treatment of refractory MSI-H metastatic colorectal cancer, 220 (3.4%) received ICIs at some point during treatment.
Patients with MSI-H tumors were significantly more likely to receive ICIs vs those with microsatellite stable (MSS) tumors (odds ratio [OR] = 22.66, 95% confidence interval [CI] = 17.30–29.73, P < .001). Patients initially diagnosed with synchronous metastatic colorectal cancer were significantly less likely to receive ICIs than did those with metachronous metastatic colorectal cancer (OR = 0.57, 95% CI = 0.45–0.73, P < .001).
Patients with MSI-H tumors who received ICIs as first-line therapy had significantly longer overall survival than did those who received chemotherapy alone (hazard ratio [HR] = 0.37, 95% CI = 0.25–0.56, P < .001).
Among patients with MSS tumors, ICI-based therapy was associated with significantly longer overall survival among patients with high vs low albumin level (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). Significantly poorer survival was observed for patients with synchronous vs metachronous metastatic colorectal cancer (HR = 1.90, 95% CI = 1.24–2.89, P = .003). Among 235 patients with MSS tumors who received ICI-based therapy, 29 (12.3%) exhibited durable responses.
The investigators concluded: “In this cohort study of patients with [metastatic colorectal cancer], 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.”
Stephanie Schmit, PhD, MPH, of the Genomic Medicine Institute, Cleveland Clinic, is the corresponding author of the JAMA Network Open article.
Disclosure: For full disclosures of the study authors, visit jamanetwork.com.
