Data Highlights Factors Impacting Immune Checkpoint Inhibitors in mCRC

Patients with microsatellite instability (MSI-H) metastatic colorectal cancer (mCRC) with immune checkpoint inhibitors (ICIs) use had a higher survival probability across different clinical characteristics.¹ Additionally, certain patients with microsatellite stable (MSS) tumors also experienced longer survival with ICIs, particularly those with high albumin levels or recent antibiotic use. These findings suggest how different clinical characteristics are associated with different survival outcomes in patients with mCRC treated with ICIs.

Clinical characteristics were associated with different survival outcomes in patients treated with immune checkpoint inhibitor-based therapy. | Image credit: Corona Borealis - stock.adobe.com

The population-based study is published in JAMA Network Open.

“In this study of routine clinical practice data from US oncology practices, patients with MSI-H mCRC who received ICIs in an early line of therapy had significantly longer survival expectancy and lower likelihood of therapy discontinuation compared with those treated with chemotherapy only,” wrote the researchers of the study. “Our findings provide substantial evidence to support results from the Keynote 177 [NCT02563002] study toward higher efficacy of first-line pembrolizumab vs. chemotherapy for patients with MSI-H mCRC."

Previously, patients with heavily pretreated MSS mCRC were found to have survival benefits after using combinations based on ICIs.² The study suggests that an ICI plus a tyrosine kinase inhibitor (TKI), either with or without chemotherapy, was able to demonstrate meaningful survival improvement.

In the current study, the researchers aimed to identify factors associated with receipt of ICIs and associated survival outcomes among patients with mCRC in routine clinical practice.¹

This study analyzed deidentified data from a nationwide electronic health record–derived database, including 18,932 patients diagnosed with mCRC between January 2013 and June 2019. Eligible patients had de novo mCRC and at least 2 documented clinical visits on or after their diagnosis. Data analysis was conducted from September 2020 to April 2021. The primary exposure of interest was the receipt of ICI therapy and/or chemotherapy as part of systemic treatment for mCRC. The study's main outcomes included the likelihood of receiving ICI therapy, overall survival (OS), and time to treatment discontinuation (TTD).

Of 18,932 patients diagnosed with mCRC, the median (IQR) age at metastatic diagnosis was 64.6 (55-73.3) years, with 55.7% of patients identifying as male. Racial and ethnic distribution included 2.9% Asian, 10.6% Black or African American, 8.8% Hispanic, 65.2% White, and 21.4% of unknown race or ethnicity.

Patients with MSI-H tumors had a significantly higher likelihood of receiving ICIs compared with those with MSS tumors (OR, 22.66; 95% CI, 17.30-29.73; P < .001). Conversely, patients with synchronous mCRC had lower odds of receiving ICIs than those with metachronous mCRC (OR, 0.57; 95% CI, 0.45-0.73; P < .001).

Among patients with MSI-H tumors, first-line ICI therapy was associated with a 63% improvement in OS compared with chemotherapy alone (HR, 0.37; 95% CI, 0.25-0.56; P < .001). For patients with MSS tumors, ICI-based therapy was linked to longer OS for those with high albumin levels (HR, 0.28; 95% CI, 0.18-0.45; P < .001) and those using antibiotics (HR, 0.43; 95% CI, 0.27-0.67; P < .001), while those with synchronous mCRC experienced shorter OS (HR, 1.90; 95% CI, 1.24-2.89; P = .003). Notably, 12.3% of individuals with MSS receiving ICI therapy achieved durable responses. Similar trends were observed for TTD.

However, the researchers noted limitations, including incomplete or missing data, which may have impacted the results. Regardless, the researchers believe the study offers critical insights into tailoring treatment strategies in routine clinical practice.

“Further research is needed to better understand the potential interaction between ICIs and patient/tumor characteristics and identify additional factors that may modulate the effect of ICIs on clinical outcomes,” wrote the researchers.

References

1. Bari S, Matejcic M, Kim R, et al. Practice patterns and survival outcomes of immunotherapy for metastatic colorectal cancer. JAMA Netwk Open. 2025;8(3):e251186. doi:10.1001/jamanetworkopen.2025.1186

2. Bonavitacola J. Treatment combinations based in immune checkpoint inhibitors provide survival benefits in CRC. AJMC^®. Published December 13, 2-24. Accessed March 19, 2025. https://www.ajmc.com/view/treatment-combinations-based-in-immune-checkpoint-inhibitors-provide-survival-benefits-in-crc