Modifying factors of PD‐L1 expression on tumor cells in advanced non‐small‐cell lung cancer

• Published in: Thoracic cancer Vol. 13; no. 23; pp. 3362 - 3373
• Main Authors: Avilés‐Salas, Alejandro, Flores‐Estrada, Diana, Lara‐Mejía, Luis, Catalán, Rodrigo, Cruz‐Rico, Graciela, Orozco‐Morales, Mario, Heredia, David, Bolaño‐Guerra, Laura, Soberanis‐Piña, Pamela Denisse, Varela‐Santoyo, Edgar, Cardona, Andrés F., Arrieta, Oscar
• Format: Journal Article
• Language: English
• Published: Melbourne John Wiley & Sons Australia, Ltd 01-12-2022; John Wiley & Sons, Inc; Wiley
• Subjects: Adenocarcinoma of Lung - genetics; B7-H1 Antigen - genetics; B7-H1 Antigen - metabolism; Biomarkers; Biomarkers, Tumor - metabolism; Biopsy; Carcinoma, Non-Small-Cell Lung - drug therapy; Cloning; Humans; Immunohistochemistry; immunotherapy; Kinases; Laboratories; Ligands; lung adenocarcinoma; Lung cancer; Lung Neoplasms - drug therapy; Medical records; Metastasis; non‐small‐cell lung cancer; Original; PD‐L1 immunohistochemistry; programmed death‐ligand 1; Reproducibility of Results; Statistical analysis; Student's t-test; Tumors; Variables; PD-L1 immunohistochemistry; programmed death-ligand 1; immunotherapy; lung adenocarcinoma; non-small-cell lung cancer
• ISSN: 1759-7706; 1759-7714
• DOI: 10.1111/1759-7714.14695

Background
Programmed death ligand‐1 (PD‐L1) expression predicts immunotherapy utility in nononcogenic addictive lung adenocarcinoma (ADC). However, its reproducibility and reliability may be compromised outside clinical trials. This study aimed to evaluate factors associated with PD‐L1 expression in lung ADC.
Methods
This observational study assessed 547 tumor samples with advanced lung ADC from January 2016 to December 2020 in a single cancer institution. Tumor samples were stained by at least one approved PD‐L1 clone, SP263 (Ventana) or 22C3 (Dako), and stratified in tumor proportion score (TPS) <1%, 1–49%, or ≥50%.
Results
Of all the tumor samples, positive PD‐L1 staining was higher in poorly differentiated tumors (67.3% vs. 32.7%, p < 0.001). Analytical factors associated with a PD‐L1 high expression (TPS ≥ 50%) were the SP263 clone (19.6% vs. 8.2%, p < 0.001), time of archival tumor tissue <12 months (15.3% vs. 3.8%, p = 0.024), whenever the analysis was performed in the most recent years (2019–2020) (19.0% vs. 8.3%, p < 0.001), and whenever the analysis was performed by pathologists in the academic setting (Instituto Nacional de Cancerologia, INCan) (19.9% vs. 11.9%, p = 0.001). In the molecular analysis, EGFR wild‐type tumors had an increased proportion of PD‐L1 positive and PD‐L1 high cases (60.2% vs. 47.9%, p = 0.006 and 17.4% vs.8.5%, p = 0.004). A moderate correlation (r = 0.69) in the PD‐L1 TPS% was observed between the two different settings (INCan vs. external laboratories).
Conclusion
Clinicopathological factors were associated with an increased PD‐L1 positivity rate. These differences were significant in the PD‐L1 high group and associated with the academic setting, the SPS263 clone, time of archival tumor tissue <12 months, and a more recent period in the PD‐L1 analysis.
Programmed death ligand‐1 (PD‐L1) is an essential biomarker guiding treatment in nononcogene addicted advanced lung adenocarcinoma, and many factors may impact its reproducibility and performance. This study demonstrated an increased probability of identifying PD‐L1‐positive samples in poorly differentiated, solid predominant, and EGFR wild‐type tumors. Discrepancies were higher in evaluating the highest PD‐L1 threshold (≥50%), the subgroup with major controversy clinically due to its eligibility for immune checkpoint inhibitors in monotherapy and combined with chemotherapy.