Chemoimmunotherapy was linked with no survival advantage versus immunotherapy alone in advanced non-small cell lung cancer during the entire follow-up period.

In patients with advanced non–small cell lung cancer (aNSCLC) and high/very high anti-programmed cell death ligand 1(PD-L1) expression, evidence regarding the comparative efficacy of chemoimmunotherapy versus immunotherapy aloneis inadequate due to the lack of head-to-head clinical trials, explains Mohsin Shah, MBBS, MSCE.

“For aNSCLC, PD-L1 immunotherapy—both as monotherapy and in combination with chemotherapy—is a standard first-line anti-tumor strategy and confers favorable survival compared to conventional chemotherapy alone,” Dr. Shah says. “Using PD-L1 as a biomarker can help predict which patients will benefit from immunotherapy, with high-tumor expression of PD-(L)1 potentially responding more favorably.”

Very High PD-L1 Expression Linked With Improved Survival

While 50% or greater is employed as a cutoff for treatment with immunotherapy alone, there is emerging evidence that in patients with aNSCLC treated with immunotherapy only, very high PD-L1 expression at 90% or greater is linked with improved survival (Table). “This suggests that degree of PD-L1 positivity may also be associated with benefit from immunotherapy,” the study authors write.

Dr. Shah and colleagues conducted a cohort study, published in Clinical Lung Cancer, utilizing a nationwide EHR database to categorize newly diagnosed patients with aNSCLC with PD-L1 expression of 50% or greater who began first-line systemic therapy between October 2016 and October 2021.

The researchers were particularly interested in first-line therapy with chemoimmunotherapy or immunotherapy in patients with a PD-L1 expression of 50% or greater or 90% or greater. Kaplan-Meier curves and Cox regression were used to evaluate survival. To control for confounding, propensity score-based inverse probability of weighting (IPW) was utilized. The study team, due to nonproportionality of hazards, also estimated HRs 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 individuals with a PD-L1 expression of 90% or greater.

Characteristics of Patients at Higher Should Be Identified

“We identified 3,086 individuals who met inclusion criteria, of whom 32% received chemoimmunotherapy and 68% received immunotherapy alone,” Dr. Shah says.

Chemoimmunotherapy was linked with no survival advantage compared with immunotherapy alone throughout the follow-up period (IPW-adjusted HR [aHR], 0.98; 95% CI, 0.86-1.12), but was linked with a survival benefit during the first 6 months (aHR, 0.74; 95% CI, 0.61-0.90).

In the subgroup of patients with a PD-L1 expression of 90% or greater, chemoimmunotherapy correlated with no overall survival benefit during follow-up (aHR, 0.99; 95% CI, 0.87-1.22), but was linked with a survival advantage during the first 12 months (aHR, 0.74; 95% CI, 0.57-0.97).

“Chemoimmunotherapy was not associated with an overall benefit over immunotherapy alone, although it was associated with an early survival advantage in both the overall cohort and the subgroup of patients with a PD-L1 expression [of 90% or greater],” Dr. Shah and colleagues wrote. “Future studies should focus on identifying the characteristics of higher-risk patients who may benefit from the addition of chemotherapy.”