A Comprehensive Analysis of Programmed Cell Death Ligand-1 Expression With the Clone SP142 Antibody in Non-Small-Cell
Kazuki Takada1, Gouji Toyokawa2, Tatsuro Okamoto2
1Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Background:
Programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) have been identified as novel targets for immunotherapy, with anti-PD-1 therapy currently the standard treatment for non-small-cell lung cancer (NSCLC) patients after the failure of first-line chemotherapy treatment. The recent phase II POPLAR and phase III OAK studies showed that atezolizumab, a representative PD-L1 inhibitor, exhibited a survival benefit compared with standard therapy in patients with NSCLC.
Patients And Methods:
We examined PD-L1 expression in NSCLC using the clone SP142 of POPLAR and OAK studies. PD-L1 expression in 499 surgically resected NSCLC patients was evaluated using immunohistochemistry using SP142. We set cutoff values as 1%, 5%, 10%, and 50%.
Results:
The samples from 189 (37.9%), 119 (23.8%), 71 (14.2%), and 39 (7.8%) patients were positive for PD-L1 expression at cutoff values of 1%, 5%, 10%, and 50%, respectively. Fisher exact tests showed that PD-L1 positivity was significantly associated with male sex, smoking, advanced stage, the presence of vascular invasion, squamous cell carcinoma, and wild type epidermal growth factor receptor gene mutation status at all cutoff values. Univariate and multivariate survival analyses revealed that PD-L1-positive patients had a worse prognosis than PD-L1-negative patients only at the 1% cutoff value. Forest plot analyses showed that the 1% cutoff provided a more sensitive value for the prediction of postoperative prognosis.
Conclusion:
PD-L1 expression varied greatly according to different cutoff values. This study might be a useful reference to understand the results of POPLAR and OAK studies and to select patients likely to benefit from atezolizumab.
Insights
Programmed cell death-1 ligand-1 (PD-L1) expression in non-small-cell lung cancer (NSCLC) varies by cutoff value. A 1% cutoff for PD-L1 positivity is most sensitive for predicting worse prognosis in NSCLC patients.
Area of Science:
- Oncology
- Immunotherapy
- Biomarker Research
Background:
- Programmed cell death-1 (PD-1) and its ligand PD-L1 are key immunotherapy targets.
- Anti-PD-1 therapy is a standard treatment for advanced non-small-cell lung cancer (NSCLC).
- Atezolizumab, a PD-L1 inhibitor, showed survival benefits in NSCLC patients per POPLAR and OAK studies.
Purpose of the Study:
- To evaluate PD-L1 expression in NSCLC using the SP142 clone.
- To determine the association between PD-L1 expression and clinicopathological features.
- To identify the optimal cutoff value for PD-L1 expression in predicting NSCLC prognosis.
Main Methods:
- Immunohistochemistry using clone SP142 on 499 surgically resected NSCLC samples.
- Analysis of PD-L1 expression at cutoff values of 1%, 5%, 10%, and 50%.
- Statistical analysis including Fisher exact tests and survival analyses.
Main Results:
- PD-L1 positivity rates were 37.9% (1%), 23.8% (5%), 14.2% (10%), and 7.8% (50%).
- PD-L1 expression correlated with male sex, smoking, advanced stage, vascular invasion, squamous cell carcinoma, and wild-type EGFR.
- PD-L1 positivity predicted worse prognosis only at the 1% cutoff, which was the most sensitive for predicting postoperative prognosis.
Conclusions:
- PD-L1 expression levels and their clinical significance in NSCLC are highly dependent on the chosen cutoff value.
- The 1% cutoff for PD-L1 expression is a sensitive biomarker for predicting poor prognosis in NSCLC.
- This study provides a reference for interpreting atezolizumab trial results (POPLAR, OAK) and patient selection.
