P44.01 Clinical Predictive Markers of Response to Immunotherapy in Advanced Non-Small Cell Lung Cancer (NSCLC)

Abstract

Overweight and obesity are associated with improved overall survival (OS) and progression-free survival (PFS) in patients treated with immune checkpoint inhibitors (ICI). EPSILoN score (EPSILoN), comprised of five clinical variables (smoking, Eastern Cooperative Oncology Group (ECOG) performance status, liver metastases, lactate dehydrogenase, and neutrophil-lymphocyte ratio), is a known predictive marker of response to immune checkpoint inhibitors (ICI). This study aims to validate body mass index (BMI) and EPSILoN as predictive markers of response in frontline ICI treatment of advanced NSCLC with or without concomitant chemotherapy. Clinical trials often underrepresent minority patients and do not stratify Hispanic patients. To our knowledge, this is the first study to assess these parameters among different race and ethnic groups. Patients with advanced NSCLC who received frontline ICI were identified using the electronic medical record. PFS and OS were retrospectively evaluated and stratified based on baseline BMI and EPSILoN. Due to lack of routine LDH testing, a modified EPSILoN (mEPSILoN) was used. Log-rank tests were used to compare PFS and OS between groups, and Kaplan-Meier curves were used to report PFS and OS. Subgroup analyses were performed for race and ethnicity and corresponding BMI and mEPSILoN were recorded. Patients in each group were quantified using descriptive statistics. Thirty-six normal weight (NW) and 25 overweight and obese (OWO) patients were studied. Median PFS (mPFS) for OWO vs NW patients was 8.90 months vs 5.53 months (HR 0.54; 95% CI, 0.30-0.96; p=0.04). mPFS at 12 months was 45% for OWO patients and 23% for NW patients. Of patients with PD-L1 ≥50%, 14 patients were NW and 11 patients were OWO. Among patients with PD-L1 ≥50%, mPFS for OWO was not reached (NR) vs 6.73 months in NW patients (HR 0.23; 95% CI, 0.09-0.60; p=0.003), and the percent of patients that were PF at 12 months was 71% vs 15%. Of 56 patients with a calculable mEPSILoN, 29 patients had mEPSILoN 1 and 27 patients had mEPSILoN 2-3. Median OS for patients with mEPSILoN 1 vs 2-3 was NR vs 11.13 months (HR 0.32; 95% CI, 0.14-0.76; p=0.01) and 78% vs 49% survived at 12 months. Subgroup analyses showed that 67% vs 41% of Black Non-Hispanic patients (BNHP) vs White Non-Hispanic patients (WNHP) had mEPSILoN 2-3 while 60% vs 43% of all Black vs White patients had mEPSILoN 2-3. Twenty-two percent vs 48% of BNHP vs WNHP were OWO. OWO and lower mEPSILoN were associated with longer PFS and OS, respectively, in patients with advanced NSCLC who were treated with frontline ICI with or without concomitant chemotherapy, regardless of PD-L1 expression. These findings are consistent with studies that reported these parameters as predictive markers of response. This is the first study, to our knowledge, to evaluate these markers in frontline ICI treatment with or without chemotherapy. BNHP began ICI treatment with more advanced disease compared to WNHP. This finding is consistent when comparing all Black and White patients. Fewer BNHP were OWO vs WNHP, indicating possible poorer response to ICI. Further studies are needed to confirm these findings.