Abstract
PURPOSE: Programmed death or ligand-1 (PD-(L)1) pathway inhibitors confer improved survival as the first-line treatment for advanced non-small cell lung cancer (aNSCLC) in patients with PD-L1 expression (PD-L1 + e ≥ 50%) compared to platinum-doublet chemotherapy and have become a standard therapy. Some recent evidence suggests that among aNSCLC patients with PD-L1 + e of ≥50% receiving pembrolizumab monotherapy, very high levels of PD-L1 + e (≥90%) may be associated with better outcomes. We sought to assess whether very high PD-L1 + e (≥90%) compared to high PD-L1 + e (50%-89%) is associated with an overall survival benefit in aNSCLC patients receiving anti-PD-(L)1 monotherapies. METHODS: We conducted a single-site retrospective cohort study of aNSCLC patients who initiated PD-(L)1 inhibitor monotherapy as the first-line treatment from October 24, 2016, to August 25, 2021, and had a PD-L1 + e ≥ 50%. The primary outcome was overall survival, measured from the start of the first-line PD-(L)1 inhibitor monotherapy (index date) to date of death or last confirmed activity prior to the cohort exit date. Propensity score-based inverse probability weighting (IPW) was used to control for confounding in Kaplan-Meier curves and Cox proportional hazard regression analysis. RESULTS: One hundred sixty-six patients with aNSCLC receiving PD-(L)1 inhibitor monotherapy met inclusion criteria. 54% were female, 90% received pembrolizumab, median age was 68 years, 70% had non-squamous cell carcinoma, 94% had a history of smoking, 29% had a KRAS mutation, and 37% had very high PD-L1 + e. Unweighted covariates at cohort entry were similar between groups (absolute standardized mean differences [SMDs] <0.1) except for race (SMD = 0.2); age at therapy initiation (SMD = 0.13); smoking status (SMD = 0.13), and BRAF mutation status (SMD = 0.11). After weighting, baseline covariates were well balanced (all absolute SMDs <0.1). In the weighted analysis, having a very high PD-L1 + e was associated with lower mortality (weighted hazard ratio 0.57, 95% CI 0.36-0.90) and longer median survival: 3.85 versus 1.49 years. CONCLUSIONS: Very high PD-L1 + e (≥90%) was associated with an overall survival benefit over high PD-L1 + e (50%-89%) in patients receiving the first-line PD-(L)1 inhibitor monotherapy in a model controlling for potential confounders. These findings should be confirmed in a larger real-world data set.