PD-L1 expression, EGFR and KRAS mutations and survival among stage III unresected non-small cell lung cancer patients: a Danish cohort study

Abstract

Abstract Programmed cell death receptor ligand-1 (PD-L1) expression, KRAS (KRASm) and EGFR (EGFRm) mutations may influence non-small cell lung cancer (NSCLC) prognosis. We aimed to evaluate PD-L1 expression, KRASm, and EGFRm and survival among stage III unresected NSCLC patients. Using Danish registries, we collected data on stage III unresected NSCLC patients diagnosed 2001–2012 and paraffin-embedded tumor tissue from pathology archives. We assessed PD-L1 expression in tumors and tumor-infiltrating immune cells (ICs) by immunohistochemistry ( $$\ge$$ ≥ 1% threshold for PD-L1+). We genotyped KRAS and EGFR. Follow-up extended from 120 days post-diagnosis to death, emigration, or 31/12/2014. We computed median survival using Kaplan–Meier methods, and hazard ratios (HRs) using Cox regression associating the biomarkers with death, adjusting for confounders. Among 305 patients, 48% had adenocarcinoma; 38% squamous cell carcinoma. Forty-nine percent had PD-L1+ tumors—51% stage IIIA and 26% KRASm. Few (2%) patients had EGFRm. Median survival in months was 14.7 (95% CI = 11.8–17.9) and 13.4 (95% CI = 9.5–16.3) in PD-L1+ and PD-L1− tumors, respectively. KRASm was not associated with death (HR = 1.06, 95% CI = 0.74–1.51 versus wildtype). PD-L1+ tumors yielded a HR = 0.83 (95% CI = 0.63–1.10); PD-L1+ ICs a HR = 0.51 (95% CI = 0.39–0.68). Tumor expression of PD-L1 did not influence survival. PD-L1+ ICs may confer survival benefit in stage III unresected NSCLC patients.