Dr Ricciuti on PD-L1 Expression and Long-Term Survival Outcomes With PD-L1 Inhibitors in Advanced NSCLC

Biagio Ricciuti, MD, thoracic medical oncologist, staff scientist II, Department of Medicine, Dana-Farber Cancer Institute, discusses the association between PD-L1 expression levels and long-term survival with anti–PD-L1 monotherapy in patients with advanced non–small cell lung cancer (NSCLC).

At the International Association for the Study of Lung Cancer (IASLC) 2023 World Conference on Lung Cancer, Ricciuti presented 3-year outcomes and correlative analyses from 2 independent cohorts of patients with advanced NSCLC and a PD-L1 tumor proportion score (TPS) of 50% or greater who have previously received PD-1 inhibition.

Initial data from these analyses showed that patients with a very high PD-L1 expression level (TPS of 90%-100%) had better clinical outcomes with first-line pembrolizumab (Keytruda) vs those with a lower PD-L1 expression level (TPS of 50%-10%), Ricciuti details.However, there were no data with long-term outcomes in among patients with high PD-L1 expression levels (50-89%) vs very high (90% or greater) PD-L1 expression within this population, he notes.

Analysis of 3-year survival outcomes for patients treated with cemiplimab (Libtayo) in the phase 3 EMPOWER-Lung-1 trial (NCT03088540) revealed that those with high PD-L1 expression levels exhibited lower response rates and shorter median progression-free survival and overall survival compared with patients who have very high PD-L1 expression, Ricciuti reports.

Patients in the validation group who received pembrolizumab did not experience a significant difference in survival outcomes at the 3-year mark between low and high PD-L1 expression groups, Ricciuti adds.

Moreover, patients with very high PD-L1 TPS had a lower prevalence of STK11/SMARCA4 mutations and increased CD8-positive/PD-1–positive T cells, indicating a more favorable genomic and immunophenotypic profile.

These findings confirm that PD-1 monotherapy provides long-term survival benefit for patients with advanced NSCLC and very high PD-L1 expression. Long-term outcomes suggest that PD-1 monotherapy can be a reasonable treatment alternative for patients with very high PD-1 expression levels (90% to 100%) compared to chemo-immunotherapy, potentially sparing them from the added toxicity of chemotherapy, Ricciuti concludes.