Association of PD-L1 tumor proportion score=20% with early resistance to osimertinib in patients with EGFR-mutated NSCLC

Background: The relationship between epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance, including osimertinib, and programmed cell death-ligand 1 (PD-L1) expression status in EGFR-mutated non-small cell lung carcinoma (NSCLC) remains unclear.Patients and Methods: We retrospectively analyzed 64 patients with unresectable advanced or metastatic NSCLC carrying EGFR exon 19 deletions (ex19del) or EGFR exon 21 L858R substitutions (L858R) who received osimertinib as the first-line treatment. We compared progression-free survival (PFS) between eligible patients with PD-L1 tumor proportion scores (TPS) = 20% and PD-L1 TPS <20% using the Kaplan- Meier survival plots with a log-rank test. Multivariate analysis was performed to examine the poor prognostic factors of PFS.Results: The PD-L1 TPS = 20% group included 22 cases (median [range] age: 70.5 [33- 86] years; 10 women [45.5%]; 11 current or ex-smokers [50%]); ECOG performance status (PS) of 0- 1/2/3/4 was noted in 16/4/1/1 patients, respectively. The PD-L1 TPS <20% group included 42 patients (median [range] age 73 [43- 88] years; 29 women [69%]; 12 current or ex-smokers [28.6%]); ECOG PS of 0- 1/2/3/4 was noted in 33/6/3/0 cases, respectively. The median PFS was 9.1 and 28.1 months in the PD-L1 TPS =20% and PD-L1 TPS <20% groups, respectively (log-rank p=0.013). Multivariate analysis revealed that PD-L1 TPS =20% was associated with PFS (hazard ratio: 2.35, 95% confidence interval: 1.09- 5.08, p = 0.030).Conclusion: PD-L1 TPS >_20% in patients with EGFR-mutated NSCLC may be associated with early resistance to osimertinib.