Digital Versus Manual PD-L1 Scoring in Advanced NSCLC From the IMpower110 and IMpower150 Trials

• Published in: Journal of thoracic oncology
• Main Authors: Herbst, Roy S., Prizant, Hen, Ruderman, Daniel, Conway, Jake, Shamshoian, John, Koeppen, Hartmut, Zou, Wei, de Marinis, Filippo, Giaccone, Giuseppe, Jassem, Jacek, Spigel, David R., Socinski, Mark A., Reck, Martin, Molinero, Luciana, Ballinger, Marcus, Shames, David, Griffin, Michael, Yu, Limin, Agrawal, Nishant, Beck, Andrew, Wapinski, Ilan, Hennek, Stephanie, Giltnane, Jennifer, Srivastava, Minu K.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.08.2025
• Subjects: Advanced or metastatic NSCLC; AIM-PD-L1; Digital pathology; Non–small cell lung cancer; AIM-PD-L1; Advanced or metastatic NSCLC; Digital pathology; Non–small cell lung cancer
• ISSN: 1556-0864; 1556-1380
• DOI: 10.1016/j.jtho.2025.07.131

Treatment selection in patients with advanced NSCLC is based on programmed death-ligand 1 (PD-L1) expression, which is usually scored manually and is subject to intra- and inter-pathologist variability. A PD-L1 clone-agnostic artificial intelligence (AI) model for AI-based measurement of PD-L1 (AIM-PD-L1) was developed and assessed in advanced NSCLC using clinical samples from two phase 3 trials. IMpower110 evaluated atezolizumab versus chemotherapy in PD-L1–positive metastatic, stage IV, squamous or nonsquamous NSCLC. IMpower150 evaluated atezolizumab, carboplatin, and paclitaxel, with or without bevacizumab, versus carboplatin, paclitaxel, and bevacizumab in patients with metastatic nonsquamous NSCLC. AIM-PD-L1 was developed and deployed on SP263-stained whole slide images (IMpower110, n = 509; IMpower150, n = 766) for digital scoring of tumor cell (TC) PD-L1 expression and identification of human-interpretable features (HIFs) associated with survival outcomes. Overall percentage agreements between scoring methods for TC more than or equal to 50% and more than or equal to 1% cutoffs were high. Survival analyses were similar for PD-L1 subgroups between scoring methods at both TC cutoffs. A nonsignificant improvement in survival outcomes was observed in patients treated with atezolizumab-containing regimens and classified as positive by digital scoring but missed by manual scoring. Two HIFs in the cancer epithelium—density of all PD-L1–positive TC and immune cells—were nominally associated with overall survival. Many HIFs were identified to be predictive of significantly improved progression-free survival with atezolizumab-containing regimens versus control. AIM-PD-L1 digital SP263 PD-L1 scoring is concordant with manual scoring, revealing similar predictivity for benefit, and could potentially be used as a predictive marker for patient stratification and selection for anti–PD-(L)1 therapy. [Display omitted]