Abstract 2017: Association of digital and manual quantification of tumor PD-L1 expression with outcomes in nivolumab-treated patients

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 < 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 < 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 (0.36–0.7