1188 Comparative differences of irAE between extensive stage small cell lung cancer and non-small cell lung cancer

<h3>Background</h3> Lung cancer is the leading cause of cancer-related death. In most studies evaluating lung cancer treatment outcomes, extensive stage small cell lung cancer (ES-SCLC) and non-small cell lung cancer (NSCLC) are described separately due to significant differences in their risk factors, pathology, treatment, and mortality. However, both types of lung cancer are now treated with immune checkpoint inhibitors (ICI), which may cause immunotherapy-related adverse events (irAE). This study aimed to compare irAE between ES-SCLC and NSCLC, given their similar primary anatomy but distinct histology, to potentially shed light on underlying mechanisms. <h3>Methods</h3> We created an IRB-approved retrospective registry of all patients who received at least one dose of an ICI for ES-SCLC or NSCLC between 2/1/2011 and 4/7/2022 at a comprehensive cancer center and its outreach clinics. Study personnel reviewed electronic medical records and categorized irAEs according to the Common Terminology Criteria for Adverse Events. Research specialists at Vasta Global captured most clinical outcomes. Bivariate comparisons were made using Chi-squared or Fisher’s exact test for categorical variables and two-sample T-test or Wilcoxon rank sum test for continuous variables. Survival analysis was performed using the Fine and Gray model for competing risks between irAE and death. <h3>Results</h3> The final cohort included 1,358 patients, 244 (18%) of whom were diagnosed with SCLC. SCLC patients were younger (mean (SD): 62.2 (9.6) vs. 64.5 (9.9) years old; p=0.001), more often female (54% vs. 43%; p=0.002), and more likely to have smoked tobacco (never smoked 2.9% vs. 7.5%; p=0.003). There were no significant differences in the presence of specific comorbidities between patients with ES-SCLC vs. NSCLC, including asthma (15.6% vs. 12.2%) and COPD (63.9% vs. 64.9%); p &gt; 0.05. ES-SCLC patients were significantly less likely to experience irAE pneumonitis (2.87% vs. 9.25%; p &lt; 0.01) or renal injury (0% vs. 1.7%; p = 0.04). When modeled using competing risk for death, controlling for age, sex, and smoking history, ES-SCLC patients had a significantly lower hazard of any irAE than NSCLC (HR = 0.64; 95% CI [0.48–0.85]). <h3>Conclusions</h3> Patients with ES-SCLC had a significantly lower hazard of experiencing immunotherapy-related adverse events (irAEs) compared to those with NSCLC. This difference persisted even after adjusting for age, sex, and smoking history. This finding merits further comparative study, given SCLC typically has higher mitotic activity, whereas NSCLC may histologically be a closer representation of native lung tissue. <h3>Ethics Approval</h3> This study was approved by the Wake Forest IRB study number:00044126. Informed consent was waived by the IRB given the retrospective, de-identified nature of the data.