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. 2024 Apr;15(11):895-905.
doi: 10.1111/1759-7714.15244. Epub 2024 Mar 8.

Association of PD-L1 expression with driver gene mutations and clinicopathological characteristics in non-small cell lung cancer: A real-world study of 10 441 patients

Gonzalo Ruiz  1 , Diego Enrico  2   3 , Yamil D Mahmoud  4   5 , Alan Ruiz  1 , María Florencia Cantarella  1 , Laura Leguina  1 , Mariana Barberis  1 , Asunción Beña  1 , Esteban Brest  1 , Solange Starapoli  1 , Andrea Mendoza Bertelli  1 , Florencia Tsou  2   3 , Carmen Pupareli  2   3 , María Pía Coppola  6 , Alejandra Scocimarro  6 , Susana Sena  7 , Patricio Levit  8 , Aldo Perfetti  8   9 , Enrique Aman  10 , María Romina Girotti  1   4 , Oscar Arrieta  11 , Claudio Martín  2   3 , Rubén Salanova  1
Affiliations

Association of PD-L1 expression with driver gene mutations and clinicopathological characteristics in non-small cell lung cancer: A real-world study of 10 441 patients

Gonzalo Ruiz et al. Thorac Cancer. 2024 Apr.

Abstract

Background: Programmed death ligand-1 (PD-L1) expression is a well-known predictive biomarker of response to immune checkpoint blockade in non-small cell lung cancer (NSCLC). However, there is limited evidence of the relationship between PD-L1 expression, clinicopathological features, and their association with major driver mutations in NSCLC patients in Latin America.

Methods: This retrospective study included patients from Argentina with advanced NSCLC, and centralized evaluation of PD-L1 expression concurrently with genomic alterations in the driver genes EGFR, ALK, ROS1, BRAF, and/or KRAS G12C in FFPE tissue samples.

Results: A total of 10 441 patients with advanced NSCLC were analyzed. Adenocarcinoma was the most frequent histological subtype (71.1%). PD-L1 expression was categorized as PD-L1 negative (45.1%), PD-L1 positive low-expression 1%-49% (32.3%), and PD-L1 positive high-expression ≥50% (22.6%). Notably, current smokers and males were more likely to have tumors with PD-L1 tumor proportion score (TPS) ≥50% and ≥ 80% expression, respectively (p < 0.001 and p = 0.013). Tumors with non-adenocarcinoma histology had a significantly higher median PD-L1 expression (p < 0.001). Additionally, PD-L1 in distant nodes was more likely ≥50% (OR 1.60 [95% CI: 1.14-2.25, p < 0.01]). In the multivariate analysis, EGFR-positive tumors were more commonly associated with PD-L1 low expression (OR 0.62 [95% CI: 0.51-0.75], p < 0.01), while ALK-positive tumors had a significant risk of being PD-L1 positive (OR 1.81 [95% CI: 1.30-2.52], p < 0.01).

Conclusions: PD-L1 expression was associated with well-defined clinicopathological and genomic features. These findings provide a comprehensive view of the expression of PD-L1 in patients with advanced NSCLC in a large Latin American cohort.

Keywords: driver mutations; genomic alterations; immunohistochemistry (IHC); non‐small cell lung cancer (NSCLC); programmed death‐ligand 1 (PD‐L1).

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Conflict of interest statement

The authors declare no conflicts of interest related to this study.

Figures

FIGURE 1
FIGURE 1
Flow chart of included patients and biomarker analysis. *Patients excluded represented samples nontested or not evaluable.
FIGURE 2
FIGURE 2
Frequency of programmed death ligand‐1 (PD‐L1) expression in the total population (a). Frequency of driver oncogene alterations (EGFR, KRAS G12C, BRAF, ALK, and ROS1) according to the expression of PD‐L1 (b). *Negative tests represent tumors without EGFR, KRAS G12C, BRAF, ALK, and ROS1 alterations. Only tumors with available test analysis were included in these graphs.
FIGURE 3
FIGURE 3
Association of programmed death ligand‐1 (PD‐L1) expression in tumor cells (TPS) with clinicopathological characteristics. Statistical significance: ****p < 0.0001.
FIGURE 4
FIGURE 4
Frequency of cases harboring concomitant alteration.
See this image and copyright information in PMC

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