Real World Effectiveness of Durvalumab in Stage III Unresectable Non-small Cell Lung Cancer: What is the Role of PD-L1 Expression?

Purpose: Although the European Medicines Agency approved durvalumab post-chemoradiation (CRT) only for stage III unresectable non-small cell lung cancer (UR-NSCLC) patients with PD-L1 tumor proportion scores (TPS) ≥ 1%, the Netherlands offers reimbursement irrespective of PD-L1 status. This real-world study compares survival between durvalumab-treated patients with PD-L1 TPS < 1% vs. ≥ 1%, and also evaluates its effectiveness against a historic-cohort. Patients and Methods: This multicenter retrospective study included 2 patient cohorts with stage III UR-NSCLC: a durvalumab cohort and a historic CRT-only cohort. The durvalumab cohort was divided into PD-L1 TPS subgroups: < 1%, ≥ 1%, and unknown. Overall survival (OS) and progression-free survival (PFS) were compared between (1) durvalumab-treated patients with PD-L1 TPS < 1% vs. ≥ 1%, and (2) durvalumab cohort (including PD-L1 subgroups) vs. historic-cohort. Results: 229 and 339 patients were included in the durvalumab- and historic-cohorts, respectively. Although not statistically significant, durvalumab-treated patients with PD-L1 TPS ≥ 1% experienced a modestly greater benefit in OS (2-year OS 74.3% vs. 66.5%) and PFS (2-year PFS 55.5% vs. 36.2%) compared to those with PD-L1 TPS < 1%. Survival outcomes favored durvalumab over the historic cohort across PD-L1 subgroups, though PFS improvement was not statistically significant for PD-L1 TPS < 1%. Conclusions: Given these findings, patients with PD-L1 TPS < 1% may also benefit from durvalumab treatment in stage III UR-NSCLC.