Dronin-Fenton D, Dalvi T, Movva N, Pedersen I, Hansen H, Fryzek J, Mellemgaard A, Rasmussen T, Klein A, Hamilton-Dutoit S, Nørgaard M. PD-L1 expression and survival in stage III unresectable non-small cell lung cancer patients in Denmark. Accepted for presentation to a virtual meeting (due to COVID-19) of the European Society for Medical Oncology (ESMO), abstract #2865, August 2020.
Anti-PD-L1 therapy improves the prognosis in advanced non-small cell lung cancer (NSCLC). We examined the association between PD-L1 expression and survival in unresectable stage III NSCLC patients treated with standard of care therapy.
We obtained data on unresectable stage III NSCLC patients (defined via American Joint Committee on Cancer staging and without surgery up to 120 days after diagnosis) diagnosed from 2001 to 2012 from the Danish Lung Cancer Registry. We retrieved clinical data from Danish population-based registries and paraffin-embedded tumor tissue from pathology archives. We assessed PD-L1 expression in tumors and tumor-infiltrating lymphocytes using the Ventana IHC (SP263) validated assay (≥1% threshold for positivity). Follow-up began at time of NSCLC diagnosis and continued to death, emigration, or 31/12/2014. We used Cox regression to compute hazard ratios (HRs) and associated 95% confidence intervals (95% CIs) for the association of PD-L1 expression with death, adjusting for age, sex, histology, Charlson comorbidity score, and age of the tumor specimen.
Of 305 patients, 183 (60%) were men, 167 (55%) were >65 years at diagnosis. Overall, 148 (49%) patients had adenocarcinoma, 117 (38%) had squamous histology. 149 (49%) had PD-L1 positive tumors (≥1%). Among PD-L1 positive tumors, 51% had stage IIIA, 49% had stage IIIB disease. Among PD-L1 negative tumors, 58% had stage IIIA and 42% had stage IIIB tumors. Tumor cell positivity for PD-L1 ≥1% vs PD-L1 <1% yielded an HR=0.83 (95%CI=0.63-1.10), while PD-L1 measured as a continuous variable yielded a HR=1.00 (95%CI=0.99-1.00). Immune cell positivity for PD-L1 ≥1% yielded HR of 0.51 (95%CI=0.39-0.68), compared with PD-L1 <1% . Tumor infiltration by immune cells measured as a continuous variable yielded an HR=0.96 (95% CI=0.93-0.99).
Findings from this Danish registry-based study suggests that PD-L1 expression in tumor-infiltrating immune cells may be associated with improved survival in unresectable stage III NSCLC patients. The implications of these findings on the effectiveness of PD-1/PD-L1 immunotherapy could not be investigated in this historical cohort.