The clinical impact of three validated PD-L1 immunohistochemistry assays as a prognostic factor in small cell lung cancer

Abstract

Background: Evidence of the clinical impact of programmed death-ligand 1 (PD-L1) expression in small cell lung cancer (SCLC) is scarce and conflicting, even though atezolizumab became the first PD-L1 inhibitor approved by the US Food and Drug Administration (FDA) in recent years for the initial treatment of extensive-stage (ES)-SCLC.Methods: We investigated PD-L1 expression in SCLC tumors using the three validated PD-L1 immunohistochemistry (IHC) assays (SP263, SP142, and 22C3) and assessed the correlation between PD-L1 expression and clinicopathological factors to determine the prognostic value of PD-L1 expression. The three PD-L1 IHC analyses were prospectively used to assess tumor samples of patients with SCLC at diagnosis.Results: Of the total of 59 patients, 47 patients received the active treatment beyond platinum-based chemotherapy at our institution. PD-L1 expression was positive in 39.0% with SP263, 37.3% with SP142, and 22.0% with 22C3. In a univariate analysis, the positive result of at least one of the three PD-L1 assays and the positive result of the SP142 assay were associated with longer overall survival (OS). A multivariable analysis confirmed that performance status, stage, and the SP142 assay were independent predictors of OS.In subgroup analysis, these results revealed more significant prognostic factors in ES than in limited-stage (LS). In patients with SCLC, especially those with ES, the expression of the SP142 assay is a significant independent prognostic factor.Conclusions: Although these results need to be further validated in larger cohorts, this information will benefit clinicians and patients in determining the immunotherapy for patients with ES-SCLC.

A Systemic Immune Inflammation Index and PD-L1 (SP142) Expression as a Potential Combined Biomarker of the Clinical Benefit of Chemo-Immunotherapy in Extensive-Stage Small-Cell Lung Cancer

“…We found that the prognostic value of the SII is superior to the values of the other CBC-IBs (NLR, PLR, and MLR) in ES-SCLC. Similar to our previous finding [ 22 ], SP142 expression was significantly associated with a longer OS in patients with ES-SCLC. Furthermore, the combined SII-SP142 biomarker was better for predicting both survival and progression in patients with ES-SCLC.…”

“…To evaluate the PD-L1 expression, we used the widely used validated VENTANA PD-L1 SP142 IHC assay (Ventana Medical Systems, Inc., Tucson, AZ, USA), as previously described [ 22 ]. The PD-L1 expression in the immune cells (IC) and tumor (TC) cells was assessed in formalin-fixed paraffin-embedded tumor samples obtained via tissue biopsy at diagnosis.…”

“…Therefore, this study was conducted to investigate a new combined biomarker with prognostic or predictive value in ES-SCLC. We previously showed that PD-L1 (SP 142) expression is a more significant prognostic factor in ES-SCLC than in limited-stage SCLC [ 22 ]. Here, we determined the best independent prognostic biomarker among the four CBC-IBs.…”

Small-Cell Lung Cancer Long-Term Survivor Patients: How to Find a Needle in a Haystack?

“…Some retrospective studies showed that the expression of PD-L1 was significantly higher in early-stage SCLC than in extended disease (p = 0.011), and resulted in an independent prognostic biomarker of a favorable outcome [62][63][64]. In contrast, some studies of early stages of SCLC suggest that higher expressions of PDL-1 confer a worse prognostic in SCLC resected and that higher PDL1 expression is associated with a higher stage disease [65].…”

Small-Cell Carcinoma of the Lung: What We Learned about It?

“…Several reasons are reported, including the different clones of antibodies used, the scoring systems, the type (resection or biopsy) of specimens evaluated, the cut-off values used, and the assessment of the PD-L1 staining pattern. A study of PD-L1 clinical impact assessment in advanced stage Acta Cytologica 2022;66:257-268 DOI: 10.1159/000519688 SCLC by ICC using the 3 approved antibodies was recently conducted by Lee et al [91]. Despite the positive correlation described between PD-L1 expression and a better patient outcome, the study has several limitations regarding the tissue determination, without a clear explanation of positivity assessment or cut-off or antibodies comparison description.…”