Association Between Survival and Very High Versus High PD-L1 Expression in Patients Receiving Pembrolizumab as First-line Treatment for Advanced Non-Small Cell Lung Cancer

Abstract

Background: A prior study found that, among advanced non-small cell lung cancer (aNSCLC) patients with PD-L1 expression 50% to 100% receiving immunotherapy as monotherapy, PD-L1 expression ≥ 90% was associated with longer survival. We sought to replicate this finding using real-world data from community oncology practices across the US.

Methods: Retrospective cohort study of aNSCLC patients who initiated pembrolizumab monotherapy for first line and had a PD-L1 expression ≥ 50% using a nationwide, deidentified longitudinal electronic health record-derived real-world database. The exposure of interest was very high PD-L1 expression, which was defined as ≥ 90%, compared to high PD-L1 expression, defined as 50% to 89%. The primary outcome was overall survival, measured from initiation of pembrolizumab to date of death, with censoring at last healthcare encounter. Multiple imputation was used to impute missing covariates. Propensity score-based inverse probability weighting (IPW) was used to address confounding in Kaplan-Meier curves and Cox proportional hazard regression models.

Results: The cohort included 1952 aNSCLC patients receiving first-line pembrolizumab monotherapy. Half of cohort members were female, median age was 73 years (interquartile range, 65-80), 71% had non-squamous histology, 94% had a history of smoking, and 46% had very high PD-L1 expression. Median overall survival in the propensity score-weighted sample was 15.84 months for very high PD-L1 expression and 12.72 months for high PD-L1 expression. Having a very high PD-L1 expression was associated with lower hazard of mortality (IPW hazard ratio 0.79, 95% CI 0.69-0.91).

Conclusions: In this large national US cohort, patients with very high PD-L1 expression (≥ 90%) aNSCLC receiving first-line pembrolizumab experienced better median survival than those with high PD-L1 expression (50% to 89%).

Keywords: Immunotherapy; Inverse probability weighted; Non-small cell lung cancer; Prognostic marker; Real-world study; Survival outcomes.