Clinical and molecular characteristics associated with high PD-L1 expression in EGFR-mutated lung adenocarcinoma

Abstract

Objective: Recent evidence suggests that elevated levels of PD-L1 expression may be linked to early resistance to TKI and reduced survival in NSCLC with EGFR mutations. This study aimed to characterize the clinical and molecular features of EGFR-mutated lung adenocarcinomas and determine the prognostic significance associated with high PD-L1 expression.

Materials and methods: We conducted a retrospective chart review of 103 consecutive patients with advanced EGFR-mutated NSCLC, who received treatment between 01/01/2016 and 30/12/2020, at our institution.

Results: Among the tumors, 17% (n = 18) exhibited high PD-L1 expression (≥50% tumor proportion score), which was associated with a lower prevalence of common EGFR mutations (56% vs. 82%, p = 0.03) and a higher frequency of complex EGFR mutations (28% vs. 7%, p = 0.02). Univariate analysis did not reveal any significant differences in first-line response, progression-free survival, or overall survival between the PD-L1 ≥50% and <50% groups. However, multivariate analysis demonstrated that PD-L1 ≥50% was independently associated with shorter survival (HR = 2.57; 95%CI[1.20-5.55]; p = 0.02), along with male gender (HR = 2.77; 95%CI[1.54-4.19]; p<0.005), presence of liver metastases (HR = 5.80; 95%CI[2.86-11.75]; p<0.005) or brain metastases (HR = 1.99; 95%CI[1.13-3.52]; p = 0.02), and poor general condition at diagnosis (ECOG 3 and 4) (HR = 10.69; 95% CI[4.42-25.85]; p<0.005). Additionally, a trend towards a higher frequency of de novo resistance was observed in the PD-L1 >50% group (7% vs. 17%, p = 0.19).

Conclusion: High PD-L1 expression was more commonly found in lung adenocarcinomas with uncommon and complex EGFR mutations. Furthermore, high PD-L1 expression independently predicted poor survival. These findings warrant validation through prospective studies.

Fig 1. Study flowchart based on inclusion and exclusion criteria.

The flowchart illustrates the process of patient selection for the study, considering both inclusion and non-inclusion criteria. Initially, a total of 103 patients were included in the study after excluding those who did not meet the specified criteria.

Fig 2

Progression-free survival (A) and overall survival (B) according to PD-L1 expression. Kaplan Meier curves are shown. High PD-L1 expression is defined as TPS ≥ 50%.

Fig 3. Changes in PD-L1 levels before treatment and at progression after first-line therapy.

The figure illustrates the evaluation of PD-L1 levels in twenty patients (numbered from 0 to 20) before treatment (on the left) and the subsequent changes in PD-L1 levels after first-line therapy (on the right). Patients with a significant change (>30%) in PD-L1 levels are highlighted in red.