PD-L1 expression as a predictor of postoperative recurrence and the association between the PD-L1 expression and EGFR mutations in NSCLC

Kensuke Kojima,Takahiko Kasai,Tetsuki Sakamoto,Tomoko Kagawa,Hyungeun Yoon,Shinji Atagi

doi:10.1038/s41598-021-96938-9

Kensuke Kojima, Takahiko Kasai + Show 4 more

Open Access

https://doi.org/10.1038/s41598-021-96938-9

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Abstract

Although information on the PD-L1 expression and EGFR mutations in non-small cell lung cancer (NSCLC) is important for therapeutic strategies, the effect of these factors on postoperative recurrence and the association between each factor have remained unclear. We retrospectively assessed the PD-L1 expression and EGFR mutations in 280 NSCLC patients, and analyzed the associations by multivariate analyses. The hazard ratio (HR) of postoperative recurrence in cases with high (≥ 50%) PD-L1 expression regarding negative expression was 4.83 (95% confidence interval [CI] 1.51–15.5). The HR for the PD-L1 expression, considered a continuous variable, was 1.016 (95% CI 1.01–1.03). The HRs in cases with EGFR major and minor mutations were 0.42 (95% CI 0.14–1.25) and 0.63 (95% CI 0.18–2.15), respectively. The high PD-L1 (≥ 50%) expression was significantly associated with exon 21 L858R mutation (Ex21) of EGFR (odds ratio, 0.10; 95% CI 0.01–0.87). The risk of postoperative recurrence increased 1.016-fold for every 1% increase in the PD-L1 expression, and a marked increase in risk was observed for expression levels of ≥ 50%. Whereas EGFR mutations were not an independent risk factor. The high PD-L1 (≥ 50%) expression was negatively associated with Ex21. These findings may help identify NSCLC patients with an increased risk of postoperative recurrence.

Highlights

Information on the programmed death-ligand 1 (PD-L1) expression and epidermal growth factor receptor gene (EGFR) mutations in non-small cell lung cancer (NSCLC) is important for therapeutic strategies, the effect of these factors on postoperative recurrence and the association between each factor have remained unclear
Chi-squared tests showed that the high expression of PD-L1 was more common in male patients, smokers, the histological type of SCC and other in NSCLC, pathological stage II and IIIA, the presence of adjuvant therapy, and wild-type EGFR mutation status
The multivariate Cox proportional hazards analysis adjusted for EGFR mutation status, pathological stage, histological type, and adjuvant chemotherapy revealed that postoperative recurrence of lung cancer was 4.8 times as likely to occur with a PD-L1-high expression status in comparison to PD-L1-negative cases

Summary

Introduction

Information on the PD-L1 expression and EGFR mutations in non-small cell lung cancer (NSCLC) is important for therapeutic strategies, the effect of these factors on postoperative recurrence and the association between each factor have remained unclear. Abbreviations ADC Adenocarcinoma EGFR Epidermal growth factor receptor gene Ex19 Exon 19 deletion Ex21 Exon 21 L858R NSCLC Non-small cell lung cancer PD-L1 Programmed death-ligand 1 RFS Recurrence free survival SCC Squamous cell carcinoma. A large cohort study on postoperative patients with NSCLC suggested that the expression of PD-L1 might be a poor prognostic factor for recurrence-free survival (RFS)[7]. A large cohort study examining the association between the type of EGFR mutations and postoperative recurrence showed that patients with exon 19 deletion (Ex19) had significantly shorter postoperative RFS in comparison to those with exon 21 L858R mutation (Ex21)[8]. Regarding the association between the expression of PD-L1 and EGFR mutations in NSCLC, it has been reported that NSCLC with EGFR mutation was less likely to express PD-L1 and exhibited a poor response to ICIs in comparison to EGFR wild-type[9]

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