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

Abstract

BackgroundThe 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 MethodsWe 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.ResultsThe 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).ConclusionPD‐L1 TPS ≥20% in patients with EGFR‐mutated NSCLC may be associated with early resistance to osimertinib.

Enhancing First-Line TKI Efficacy in PD-L1-Positive EGFR-Mutated NSCLC: The Role of Antiangiogenic Agents

“…The prognostic signi cance of PD-L1 expression in EGFR-mutated NSCLC patients, particularly regarding PFS with TKI, remains an area of ongoing research. Most studies (10,11,16,17,18,19) and meta-analyses (8) have shown that patients with positive or high PD-L1 expression generally have poorer outcomes. This aligns with our ndings, which bodes ill for this group of patients.…”

“…While a majority of previous studies have designated 50% as the threshold to differentiate between high and low PD-L1 expression (9, 16), there is growing evidence of prognostic variances between PD-L1 positivity and negativity (17,29,30,31). A recent study has proposed that a 20% cut-off point might more accurately re ect these prognostic differences (10). This suggestion is particularly relevant in light of the substantial variability in PD-L1 expression detection caused by different antibodies and experimental conditions.…”

“…Current metaanalyses indicate that patients with PD-L1 positivity tend to have shorter progression-free survival (PFS) when treated with rst-line EGFR TKIs (8). This is further evidenced by various studies examining the relationship between PFS, PD-L1 expression, and the use of third-generation TKIs (9,10,11). The link between PD-L1 expression and overall survival (OS) in EGFR mutation-positive patients remains unclear.…”