A Comprehensive Analysis of Programmed Cell Death Ligand-1 Expression With the Clone SP142 Antibody in Non-Small-Cell Lung Cancer Patients

作者：Takada Kazuki; Toyokawa Gouji^*; Okamoto Tatsuro; Shimokawa Mototsugu; Kozuma Yuka; Matsubara Taichi; Haratake Naoki; Akamine Takaki; Takamori Shinkichi; Katsura Masakazu; Shoji Fumihiro; Oda Yoshinao; Maehara Yoshihiko

来源：Clinical Lung Cancer, 2017, 18(5): 572-+.

DOI：10.1016/j.cllc.2017.02.004

• Immunohistochemistry
• Immunotherapy
• Lung cancer
• Programmed cell death-1
• Programmed cell death ligand-1

We examined programmed cell death ligand-1 (PD-L1) expression in 499 surgically resected non-small-cell lung cancer (NSCLC) patients using the clone SP142 and 4 different cutoff values. PD-L1 expression in NSCLC was shown to vary greatly according to different cutoff values, and to be associated with poor survival in NSCLC patients. This study might be a useful reference to understand the results of the POPLAR and OAK studies.
Background: Programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) have been identified as novel targets for immunotherapy, with antiePD-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.

• 出版日期2017-9