Sex-based Clinical Outcome in Advanced NSCLC Patients Undergoing PD-1/PD-L1 Inhibitor Therapy - a Retrospective Bi-Centric Cohort Study

Men with non-small cell lung cancer (NSCLC) have a more favorable response to immune-checkpoint inhibitor (ICI) monotherapy, while women especially benefit from ICI-chemotherapy (CHT) combinations. To elucidate such sex differences in clinical practice, we retrospectively analyzed two cohorts treated with either ICI monotherapy (n=228) or ICI-CHT combination treatment (n=80) for advanced NSCLC. Kaplan-Meier analyses were used to calculate progression-free (PFS) and overall survival (OS), influencing variables were evaluated using Cox-regression analyses. No significant sex differences for PFS/OS could be detected in either cohort. Men receiving ICI monotherapy had a statistically significant independent impact on PFS by Eastern Cooperative Oncology Group performance status (ECOG) ≥2 (hazard ratio (HR) 1.90, 95% confidence interval (CI): 1.10-3.29, p=0.021), higher C-reactive protein (CRP; HR 1.06, 95%CI: 1.00-1.11, p=0.037) and negative programmed death-ligand 1 (PD-L1) status (HR 2.04, 95%CI: 1.32-3.15, p=0.001), and on OS by CRP (HR 1.09, 95%CI: 1.03-1.14, p=0.002). In men on ICI-CHT combinations, multivariate analyses (MVA) revealed squamous histology (HR 4.00, 95%CI: 1.41-11.2, p=0.009) significant for PFS; ECOG≥2 (HR 5.58, 95%CI: 1.88-16.5, p=0.002) and CRP (HR 1.19, 95%CI: 1.06-1.32, p=0.002) for OS. Among women undergoing ICI monotherapy, no variable proved significant for PFS, ECOG≥2 had a significant interaction with OS (HR 1.90, 95%CI 1.04-3.46, p=0.037). Women treated with ICI-CHT had significant MVA findings for CRP with both PFS (HR 1.09, 95%CI: 1.02-1.16, p=0.007) and OS (HR 1.11, 95%CI: 1.03-1.19, p=0.004). Although men and women responded similarly to both ICI mono- and ICI-CHT treatment, predictors of response differed by sex.