MO2-11-1 [Encore]Biomarkers and clinical outcomes in nivolumab-treated patients with advanced hepatocellular carcinoma in CheckMate 040. (7th October 2019)

• Record Type: Journal Article
• Authors: Melero, Ignacio; Neely, Jaclyn; Sangro, Bruno; Finn, Richard S; Abou-Alfa, Ghassan K; Cheng, Ann-Lii; Yau, Thomas; Furuse, Junji; Park, Joong-Won; Wadhawan, Samir; Tang, Hao; Anderson, Jeffrey; Boyd, Zachary; Melero, Ignacio; El-Khoueiry, Anthony
• Is Part Of: Annals of oncology. Volume 30(2019)Supplement 6
• Publication Date: 2019-10-07
• Subjects: Oncology -- Periodicals; 616.992
• DOI: 10.1093/annonc/mdz338.070
• Languages: English
• ISSNs: 0923-7534

Abstract

Abstract: Background: Nivolumab (NIVO), a programmed death-1 (PD-1) inhibitor, is approved in several countries for sorafenib-treated patients (pts) with advanced hepatocellular carcinoma (aHCC) based on CheckMate040. We report findings on exploratory biomarker analyses. Methods: In CheckMate040, pts with aHCC received NIVO regardless of programmed death ligand 1 (PD-L1) status and HCC etiology. Baseline tumor samples were analyzed by IHC for expression of PD-L1, PD-1, T-cell markers (CD3, CD4, CD8, FOXP3), and macrophages (CD68, CD163), and (in a subset of pts) by RNA sequencing for inflammatory signatures (ISs). Results were correlated with clinical outcomes: response (complete response [CR]/partial response [PR]/stable disease [SD]/progressive disease [PD]) and overall survival (OS). Associations with etiology and geographical region (non-Asia vs Asia) were assessed. Data cutoff: June 2018. Results: In 184 pts with evaluable data, increased tumor cell PD-L1 expression was associated with response (CR+PR vs SD [P = 0.00009]; CR+PR vs PD [P = 0.0007]) and OS (P = 0.03), as was increased PD-1 expression (CR+PR vs SD [P = 0.05]; CR+PR vs PD [P = 0.009]; OS [P = 0.05]). Of the T-cell markers assessed, CD3 was associated with response (n = 182, CR+PR vs SD; P = 0.05). In pts positive for CD3 or CD8, there was a trend toward improved OS (P = 0.08). There was no association between CD68 and CD163 expression and clinical outcomes. For 37 pts with RNA sequencing data available, median Bristol-Myers Squibb (BMS) IS score was higher in pts with PR vs SD (P = 0.05) and was correlated with improved OS (P = 0.01). For all inflammation markers assessed, there was no association with etiology or geographical region. Conclusions: In pts with aHCC, improved OS and response to NIVO may be associated with higher PD-L1, PD-1, and CD3 expression, and higher BMS IS scores, supporting the role of PD-1 inhibition in HCC treatment. Further investigation of these biomarkers is required. Originally presented at the AACR 2019.