Multicenter harmonization study for PD-L1 IHC testing in non-small-cell lung cancer

Area of Science:

• Oncology
• Immunohistochemistry
• Diagnostic Assays

Background:

• Multiple programmed death ligand 1 (PD-L1) immunohistochemistry (IHC) assays exist, impacting clinical trials.
• Standardization of PD-L1 testing is crucial for non-small-cell lung cancer (NSCLC) diagnosis and treatment.
• This study compares standardized PD-L1 assays with laboratory-developed tests (LDTs) in a multicenter setting.

Purpose of the Study:

• To harmonize and assess the availability of PD-L1 testing in non-small-cell lung cancer (NSCLC).
• To compare the concordance of various PD-L1 IHC assays and LDTs across different platforms and centers.
• To evaluate the analytical performance of PD-L1 assays for tumor cell and immune cell staining.

Main Methods:

• Performed IHC using five anti-PD-L1 antibodies (28-8, 22C3, E1L3N, SP142, SP263) on 41 NSCLC specimens across 7 centers.
• Utilized Dako, Leica, and Ventana platforms, developing LDTs for non-matching platforms/antibodies.
• Assessed PD-L1 staining in tumor and immune cells by seven pathologists using defined expression thresholds.

Main Results:

• PD-L1 assays 28-8, 22C3, and SP263 demonstrated high concordance for tumor cell staining across platforms.
• Of 27 developed LDTs, 14 (51.8%) showed similar concordance for tumor cell staining compared to reference assays.
• Clone SP263 exhibited the highest concordance across all platforms; immune cell staining showed lower concordance.

Conclusions:

• Standardized PD-L1 assays (28-8, 22C3, SP263) exhibit comparable analytical performance for tumor cell staining in NSCLC.
• Certain LDTs achieved good concordance, but validation is essential before widespread clinical adoption.
• Further validation of LDTs is planned to establish recommendations for PD-L1 testing in NSCLC.