Chemoimmunotherapy vs. Immunotherapy for First Line Treatment of Advanced Non–small Cell Lung Cancer With a PD-L1 Expression ≥50% or ≥90%

Background Evidence about the comparative effectiveness of chemoimmunotherapy vs. immunotherapy alone in patients with advanced non–small cell lung cancer (aNSCLC) and high PD-L1 expression (≥50%) or very high PD-L1 expression (≥90%) is limited because of the lack of head-to-head clinical trials. Objective To compare survival in aNSCLC patients receiving first-line chemoimmunotherapy vs. immunotherapy in both the PD-L1 expression ≥50% or ≥90% subgroups, accounting for potential confounders that may influence physician decision-making. Methods This cohort study used a nationwide electronic health record derived database to identify newly diagnosed cases of aNSCLC patients with PD-L1 expression of ≥50% who initiated first-line systemic therapy between October 2016 and October 2021. The exposure of interest was first-line therapy with chemoimmunotherapy or immunotherapy among patients with PD-L1 expression ≥50% or ≥90%. Survival was assessed using Kaplan-Meier curves and Cox regression. Propensity score-based inverse probability of weighting (IPW) was used to control for confounding. Because of nonproportionality of hazards, we estimated hazard ratios over the first 6 months and after 6 months for the overall cohort, and over the first 12 months and after 12 months for a subgroup of persons with a PD-L1 expression ≥90%. Results We identified 3086 subjects who met inclusion criteria, of whom 32% received chemoimmunotherapy and 68% received immunotherapy alone. Chemoimmunotherapy was associated with no survival advantage vs. immunotherapy alone during the entire follow-up period (IPW-adjusted Hazard Ratio [aHR] 0.98, 95% CI, 0.86-1.12), but was associated with a survival benefit during the first 6 months (aHR 0.74, 95% CI, 0.61-0.90). Similarly, in the subgroup of patients with a PD-L1 expression ≥90%, chemoimmunotherapy was associated with no overall survival advantage during the entire follow-up period (aHR 0.99, 95% CI, 0.87-1.22), but was associated with a survival benefit during the first 12 months (aHR 0.74, 95% CI, 0.57-0.97). Conclusion Chemoimmunotherapy was not associated with an overall benefit over immunotherapy alone, although was associated with an early survival advantage in both the overall cohort and the subgroup of patients with a PD-L1 expression ≥90%. Future studies should focus on identifying the characteristics of higher risk patients that may benefit from the addition of chemotherapy.