Comparison of programmed death-ligand 1 protein expression between primary and metastatic lesions in patients with lung cancer

Abstract

Assessment of programmed cell death-ligand 1 (PD-L1) expression by immunohistochemistry (IHC) is the definite diagnostic test to guide treatment for patients with advanced-stage non-small cell lung cancer. Intratumoral heterogeneity and discrepancy of PD-L1 expression between primary and metastatic lesions may increase the risk of tumor misclassification. We performed a retrospective study of the Foundation Medicine, Inc clinical database on lung cancer cases that were evaluated for PD-L1 expression by IHC in the context of routine care. All cases were assessed with the Food and Drug Administration-approved 22C3 pharmDx assay and scoring system. 15,028 lung cancer cases, including 8285 primary tumors and 6743 unmatched metastatic lesions were analyzed. Metastatic lesions (mets) were more frequently high positive (tumor proportion score (TPS) ≥50%) for PD-L1 expression than primary lesions (33.8% vs 28.4%; OR, 1.28; 95% CI, 1.19 to 1.37; p<0.001). Higher levels in mets than primaries were seen in samples from lymph nodes, pleural fluid, soft tissue and adrenal gland but not in those from liver, brain and bone. Metastatic lesions of patients with non-squamous histology were more likely to have TPS ≥50% in comparison with primary (OR, 1.37; 95% CI, 1.27 to 1.49; p<0.001), but this was not the case for patients with squamous histology (OR, 0.89; 95% CI, 0.74 to 1.06; p=0.197). PD-L1 expression varies with respect to histologic subtype, sampling site and gender, but is generally higher in metastatic sites. This observation may affect future patient management and trial design.

PD-L1 PET/CT imaging with radiolabeled durvalumab in patients with advanced stage non-small cell lung cancer.

“…PD-L1 expression is a biopsy-based biomarker, with the disadvantage that a small biopsy specimen does not capture the full extent of tumor heterogeneity of PD-L1 expression and is associated with a higher chance of a false negative test result [6-8 10]. In addition, substantial heterogeneity of PD-L1 expression can be observed within and between tumor lesions of the same patient [11]. As a consequence of this lack of a good predictive biomarker, the majority of patients with advanced stage NSCLC patients are treated with a PD-(L)1 checkpoint inhibitor, with or without chemotherapy [2 5].…”

Immune Checkpoint Inhibitors for Brain Metastases in Non-Small-Cell Lung Cancer: From Rationale to Clinical Application

“…there was heterogeneity of PD-L1 expression between NSCLC and BM in some patients, the PD-L1 expression between PT and BM is concordant in most patients [20,51,52]. There may be less heterogeneity in synchronous patients [20,53].…”

Immunotherapy in Lung Cancer: Current Landscape and Future Directions

“…Inter-tumor and intra-tumor heterogeneity of PD-L1 expression, a wide variety of PD-L1 assays and cutoff values utilized to define PD-L1 positivity, and the effect of handling and storage of tumor tissue on PD-L1 analysis render it an imperfect biomarker (11,(49)(50)(51)(52). Studies have shown significant discordance in PD-L1 expression between lung biopsies and corresponding resected tumors, between primary and metastatic sites, and among different metastatic sites (53)(54)(55). Finally, SCLC remains an invincible enemy with only a limited success achieved with incorporation of currently available ICIs in the treatment paradigm, largely driven by an immunosuppressive tumor microenvironment (TME) (56).…”