Abstract 2017: Association of digital and manual quantification of tumor PD-L1 expression with outcomes in nivolumab-treated patients
Authors: Duan Chunzhe , Montalto Michael , Lee George , Pandya Dimple , Cohen Daniel , Chang Han , Tang Hao , Agrawal Nishant , Elliott Hunter , Glass Benjamin , Wapinski Ilan , Edwards Robin , Beck Andrew H. , Baxi Vipul 
Published: September 2020

Abstract
Background: Programmed death ligand 1 (PD-L1) expression on tumor cells (TC), detected by immunohistochemistry (IHC), is associated with response to programmed death-1 (PD-1)/PD-L1 inhibitors in some tumor types. Manual review of PD-L1–positive (PD-L1+) tumors can be subjective, with the potential for misclassification of PD-L1–low tumors as PD-L1–negative due to weak positivity. We compared artificial-intelligence (digital) and manual scoring methods and assessed the association of PD-L1 expression with clinical outcomes in nivolumab (NIVO)-treated patients with urothelial carcinoma (UC) and melanoma (MEL).
Methods: PD-L1 expression was determined in baseline samples from NIVO monotherapy-treated patients with UC (CM275, NCT02387996) and MEL (CM067, NCT01844505; CM238, NCT02388906) using the Dako PD-L1 IHC 28-8 pharmDx assay. PD-L1+ TC were scored using digital (PathAI research platform) and manual (LabCorp) methods. Prevalence of tumors with PD-L1+ TC ≥ 1% and ≥ 5% and associations between PD-L1 expression and outcomes with NIVO were evaluated.
Results: Prevalence of UC and MEL tumors with ≥ 1% and ≥ 5% PD-L1+ TC was higher for digital vs manual scoring (Table). For all samples, digital and manual scoring was associated with response to NIVO for PD-L1 ≥ 1% and ≥ 5%, and associations were similar between digital and manual scoring (Table). Digital and manual PD-L1 scoring correlated across samples from all trials (Kendall's tau range: 0.57–0.62).
TablePrevalence PD-L1+ TC ≥ 1%, n (%)Evaluable samples, nDigitalManualP valueSamples ≥ 1% by digital onlyCM275241166 (69)113 (47)1.61 × 10−658 (24)CM067264173 (66)160 (61)0.27936 (14)CM238377307 (81)259 (69)7.61 × 10−566 (18)PD-L1+ TC ≥ 1% vs &lt; 1%DigitalManualORR, odds ratio (95% CI)CM275a2.15 (0.98–4.70)1.60 (0.82–3.14)CM067b1.99 (1.19–3.35)1.89 (1.12–3.18)Survival, hazard ratio (95% CI)CM275 (OS)a0.67 (0.48–0.92)0.66 (0.48–0.90)CM067 (OS)b0.57 (0.41–0.80)0.71 (0.50–1.00)CM238 (RFS)c0.53 (0.36–0.77)0.83 (0.57–1.21)Prevalence PD-L1+ TC ≥ 5%, n (%)Evaluable samples, nDigitalManualP valueSamples ≥ 5% by digital onlyCM27524190 (37)74 (31)0.14928 (12)CM067264103 (39)76 (29)0.01736 (14)CM238377234 (62)139 (37)7.54 × 10−12104 (28)PD-L1+ TC ≥ 5% vs &lt; 5%DigitalManualORR, odds ratio (95% CI)CM275a3.50 (1.76–6.98)2.37 (1.18–4.73)CM067b2.33 (1.40–3.86)1.77 (1.01–3.09)Survival, hazard ratio (95% CI)CM275 (OS)a0.50 (0.36–0.71)0.58 (0.41–0.83)CM067 (OS)b0.67 (0.47–0.96)0.74 (0.51–1.09)CM238 (RFS)c0.50 (0.35–0.70)0.52 (0.36–0.76)Database lock 2019: CM275, June 14; CM067, January 18; CM238, April 3.aAdjusted for ECOG performance status, liver metastatic status, and hemoglobin.bAdjusted for ECOG performance status, liver metastatic status, lactate dehydrogenase, and BRAF mutation.cAdjusted for ECOG performance status, AJCC stage, lactate dehydrogenase, and BRAF mutation.AJCC, American Joint Committee on Cancer; CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; ORR, objective response rate; OS, overall survival; PD-L1, programmed death ligand 1; RFS, recurrence-free survival; TC, tumor cells.
Conclusion: In post-hoc exploratory analyses, digital scoring of PD-L1 expression identified higher prevalence of PD-L1+ tumors and shows good association with response to NIVO in UC and MEL samples compared with manual scoring. Digital quantification demonstrated higher sensitivity at low levels of PD-L1 expression and may identify patients who could benefit from NIVO. Further study of the association with clinical outcomes is warranted and exploratory studies are ongoing to assess the performance of digital scoring in additional tumor types.
Citation Format: Chunzhe Duan, Michael Montalto, George Lee, Dimple Pandya, Daniel Cohen, Han Chang, Hao Tang, Nishant Agrawal, Hunter Elliott, Benjamin Glass, Ilan Wapinski, Robin Edwards, Andrew H. Beck, Vipul Baxi. Association of digital and manual quantification of tumor PD-L1 expression with outcomes in nivolumab-treated patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2017.