Clinical Interchangeability of PD-L1 Immunohistochemistry Assays in First-Line Non-Small Cell Lung Cancer Management With Cemiplimab.

Purpose: Multiple immunohistochemistry (IHC) assays targeting PD-L1 have been developed independently, and a lack of harmonization creates undue complexity for clinicians who use PD-L1 tests to guide treatment decisions. This novel bridging study demonstrates the clinical interchangeability of two PD-L1 IHC assays in first-line treatment of non-small cell lung cancer (NSCLC) with PD-L1 ≥50%.

Methods: In the phase III EMPOWER-Lung 1 study (ClinicalTrials.gov identifier: NCT03088540), 710 patients were randomly assigned 1:1 to first-line cemiplimab or platinum-doublet chemotherapy for advanced NSCLC with PD-L1 ≥50%, selected by PD-L1 IHC 22C3 pharmDx (Agilent Technologies, Santa Clara, CA).

Results: A total of 871 patient samples were retrospectively tested using the VENTANA PD-L1 (SP263) assay (Roche Diagnostics, Indianapolis, IN), including 481 enrolled patients and 390 patients who did not pass screening (22C3 PD-L1 <50%). Concordance of 22C3 and SP263 was evaluated in 768 patient samples, with an overall percent agreement (concordance) of 88% between the two assays. Overall survival (OS) and progression-free survival (PFS) were estimated in the PD-L1 ≥50% SP263+ population (including the 22C3+/SP263+ and 22C3-/SP263+ subpopulations). In the primary analysis, the clinical efficacy of cemiplimab versus chemotherapy in the 22C3+/SP263+ population (n = 324; OS hazard ratio [HR], 0.52 [95% CI, 0.34 to 0.80]; PFS HR, 0.43 [95% CI, 0.32 to 0.59]) was similar to that in the 22C3+ population (n = 563). A sensitivity analysis of the overall SP263+ population showed consistent results with the primary analysis.

Conclusion: Similar efficacy (OS and PFS) was observed with the 22C3+ and SP263+ populations, demonstrating the interchangeability of these PD-L1 IHC assays for selecting patients with PD-L1 ≥50% for first-line cemiplimab monotherapy for advanced NSCLC.