Real-world PD-L1 testing and distribution of PD-L1 tumor expression by immunohistochemistry assay type among patients with metastatic non-small cell lung cancer in the United States.

Background: The anti-programmed death receptor-1 (anti-PD-1) pembrolizumab is approved as first-line monotherapy for metastatic non-small cell lung cancer (mNSCLC) with PD-ligand 1 (PD-L1) tumor expression ≥50%. Most studies comparing PD-L1 results by immunohistochemistry (IHC) assay type have been conducted by prespecified and, in most cases, highly experienced, trained pathologists; however, knowledge is limited regarding the current use and concordance of PD-L1 assays in the real-world clinical setting. Our aim was to study the distribution of PD-L1 tumor expression by IHC assay type among patients with mNSCLC in US oncology practices.
Methods: This retrospective observational study utilized de-identified, longitudinal data from a large US electronic medical record database. Eligible patients were adults (≥18 years) with histologically/cytologically confirmed initial diagnosis of metastatic or recurrent NSCLC from October 2015 through December 2017. We determined PD-L1 testing trends and distribution of PD-L1 tumor expression (percentage of tumor cells staining for PD-L1) by IHC assay type.
Results: The 12,574 eligible patients (mean age, 69 years) included 6,620 (53%) men and 86% with positive smoking history. Of 4,868 evaluable tests, 3,799 (78%), 195 (4%), 165 (3%), and 709 (15%) used the Agilent 22C3 pharmDx, Agilent 28-8 pharmDx, Ventana PD-L1 (SP142) Assay, and laboratory-developed tests (LDTs, including SP263), respectively. The percentages of tests scoring PD-L1 tumor expression of ≥50% were 33%, 32%, 10%, and 23%, respectively. Measured PD-L1 tumor expression varied across the four assay types (χ2 p < 0.001) and across three assay types excluding SP142 (p < 0.001), with no significant difference between 22C3 and 28-8 assays (p = 0.96). The PD-L1 testing rate increased from 18% in the fourth quarter of 2015 to 71% in the fourth quarter of 2017.
Conclusions: In the real-world clinical setting, we observed that measured PD-L1 tumor expression is concordant using the 22C3 and 28-8 assays; however, the SP142 assay and LDTs appear discordant and could underestimate high PD-L1 positivity. Further study is needed to evaluate the association between PD-L1 tumor expression and response to therapy.
Competing Interests: Vamsidhar Velcheti has served in an advisory/consultant role for Merck & Co., Inc., Kenilworth, NJ, USA; BMS; Genentech; AstraZeneca; Celegene; Novartis; Amgen; Fulgent Genetics; Foundation Medicine. Frank Xiaoqing Liu, Xin Chen, and Thomas Burke are employees and own stock of Merck & Co., Inc., Kenilworth, NJ, USA. Pallavi D. Patwardhan and Xiting Cao were employees of Merck & Co., Inc., Kenilworth, NJ, USA, at the time of the study. Co., Inc., Kenilworth, NJ, USA. Pallavi D. Patwardhan and Xiting Cao were employees of Merck & Co., Inc., Kenilworth, NJ, USA, at the time of the study. This does not alter our adherence to PLOS ONE policies on sharing data and materials.