Propensity-matched analysis of immunotherapy alone vs chemotherapy alone in stage II-IV colon cancer: Impact on cardiovascular, renal, and metastatic risks.

Abstract

e15610 Background: Immune checkpoint inhibitors (ICIs) have revolutionized MSI-H/dMMR metastatic (stage IV) colon cancer treatment, but their real-world safety and comparative outcomes against chemotherapy alone remain unclear, especially in non-metastatic (stage II-III) disease. ICIs are not standard for stage II-III patients, and their role is under investigation. Prior studies often included combination therapies or lacked propensity-matched comparisons of ICI monotherapy vs. chemotherapy alone. This study used ICI or chemotherapy alone group comparisons to prevent overlap bias and evaluates major adverse cardiovascular events (MACE), major adverse kidney events (MAKE), liver metastases, and gastrointestinal (GI) bleeding in stage II-IV colon cancer patients. Methods: This retrospective cohort study used the TriNetX database (2017–2022) to identify stage II-IV colon cancer patients treated with ICI monotherapy (nivolumab, pembrolizumab, or atezolizumab) or fluoropyrimidine-based chemotherapy (5-FU or capecitabine). Propensity score matching (1:1) controlled for age, sex, race, comorbidities, and cancer stage. Patients with ≥3 years of follow-up were included. Median follow-up was 679 days (IQR: 810) for ICIs and 895.5 days (IQR: 710) for chemotherapy. Kaplan-Meier analysis assessed MACE, MAKE, liver metastases, and GI bleeding, with hazard ratios (HRs) and 95% confidence intervals (CIs) quantifying risks. MMR status was unavailable, limiting biomarker-specific analysis. Results: After matching, each cohort had 342 patients (mean age: 66.8 vs. 67.7 years, male: 50.29% vs. 49.12%). Median overall survival (OS) was shorter in the ICI monotherapy group (988 days vs. chemotherapy alone, HR: 1.433, 95% CI: 1.139–1.803, p = 0.0281). MAKE risk was higher with ICIs (HR: 1.406, 95% CI: 1.082–1.828, p = 0.0417), while MACE risk was comparable (HR: 1.168, p = 0.7262). Liver metastases were lower in the ICI group (HR: 0.952, 95% CI: 0.739–1.227, p = 0.0059), while GI bleeding risk showed no significant difference (HR: 0.841, p = 0.6200). Conclusions: This first propensity-matched study comparing ICI monotherapy vs. chemotherapy alone in stage II-IV colon cancer found ICIs were associated with fewer liver metastases but an increased risk of renal complications and potentially shorter survival. The survival discrepancy may reflect patient selection bias, follow-up duration, or limited ICI efficacy in certain subsets. These findings highlight the need for careful patient selection, renal monitoring, and further research on predictive biomarkers and combination strategies to optimize outcomes.