The impact of immunotherapy versus chemotherapy on mortality and adverse events in cancer patients hospitalized with septic shock.

2653 Background: Traditionally, chemotherapies have been associated with well-characterized toxicity profiles and adverse events. Meanwhile, immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but their secondary toxicities, particularly in patients with septic shock, remain underexplored. Our study sought to evaluate the comparative risk of mortality and adverse events in patients treated with ICIs versus chemotherapy. Methods: Using the TriNetX Research Database, we identified cancer patients (≥18 years) diagnosed with septic shock between January 1, 2013, and December 16, 2024. Eligible cancers included malignancies of the oral cavity, pharynx, larynx, stomach, kidney, bladder, skin, head, neck, and lung. Patients treated with ICIs or chemotherapy within 6 weeks before or up to 2 weeks after septic shock diagnosis were stratified into two cohorts. Propensity score matching (1:1) adjusted for confounders. Kaplan-Meier log-rank tests analyzed outcomes. Primary outcomes were mortality at 30, 60, and 90 days. Secondary outcomes included irAEs, organ failure, and hospitalization or emergency services within 1 week to 1 month. Results: Through our study we identified 44,052 cancer patients diagnosed with septic shock. A total of 4,284 patients were on chemotherapy within the time of their diagnosis, while 472 patients were on ICIs. ICI use was associated with higher 30-day (HR: 1.27, 95% CI: 1.03-1.57, p = 0.02), and 90-day (HR: 1.21, 95%CI: 1.009-1.45, p = 0.03) mortality. But only a near significant difference was noted at 60-days (HR: 1.20, 95%CI: 0.99-1.45, p = 0.054). Additionally, the risk of organ failures (HR: 1.28, 95%CI: 1.11-1.48,p < 0.001) and hospitalization or usage of emergency services (HR: 1.35, 95%CI: 1.16-1.56, p < 0.001) was higher in patients treated with ICIs compared to chemotherapy. The frequency of irAEs was slightly higher in patients with ICIs, though these results were only near significant (HR: 1.155, 95%CI: 0.977-1.364, p = 0.0532). Conclusions: Cancer patients treated with ICIs with septic shock exhibited higher short-term mortality, organ failure rates, and hospitalization or emergency service usage compared to those receiving chemotherapy. These findings are unexpected, given the perceived safety profile of immunotherapy compared to traditional chemotherapy. Further research is warranted to better understand these risks and to develop strategies for mitigating adverse outcomes in this population. Log-Rank Test HR 95% CI P-Value χ2 Primary Outcomes 30-day Mortality 1.272 (1.032,1.569) 0.0231 0.233 60-day Mortality 1.203 (0.996,1.452) 0.054 3.714 90-day Mortality 1.212 (1.009,1.455) 0.039 4.262 Secondary Outcomes Frequency of irAEs 1.155 (0.977,1.364) 0.0532 3.737 Incidence of organ failure 1.285 (1.115,1.48) < 0.0001 23.556 Hospitalization or emergency services 1.349 (1.165,1.562) < 0.0001 22.937