Scientific publications

Association of inflammatory biomarkers with clinical outcomes in nivolumab-treated patients with advanced hepatocellular carcinoma

Jul 22, 2020 | Magazine: Journal of Hepatology

Bruno Sangro 1 , Ignacio Melero 2 , Samir Wadhawan 3 , Richard S Finn 4 , Ghassan K Abou-Alfa 5 , Ann-Lii Cheng 6 , Thomas Yau 7 , Junji Furuse 8 , Joong-Won Park 9 , Zachary Boyd 3 , Hao Tracy Tang 3 , Yun Shen 3 , Marina Tschaika 3 , Jaclyn Neely 3 , Anthony El-Khoueiry 10

Background & aims: Nivolumab, a programmed death (PD)-1 (PD-1) inhibitor, demonstrated durable responses, manageable safety, and increased survival in patients with advanced hepatocellular carcinoma (HCC). Our retrospective analysis studied the immunobiology and potential associations between biomarkers and nivolumab outcomes in HCC.

Methods: Fresh and archival tumour samples from dose-escalation and -expansion phases of CheckMate 040 were analysed by immunohistochemistry and RNA sequencing to assess several inflammatory gene expression signatures, including CD274 (PD-L1), CD8A, LAG3, and STAT1. Biomarkers were assessed for association with clinical outcomes (best overall response [BOR] by blinded independent central review [BICR] per RECIST v1.1 and overall survival [OS]).

Results: Complete or partial tumour responses were observed in PD ligand 1 (PD-L1)-positive and -negative patients treated with nivolumab monotherapy. Median OS was 28.1 (95% CI 18.2-n.a.) vs. 16.6 months (95% CI 14.2-20.2) for patients with tumour PD-L1 ≥1% vs. <1 % (p = 0.03). Increased CD3 and CD8 showed a non-significant trend towards improved OS (both p = 0.08), and macrophage markers were not associated with OS.

Tumour PD-1 and PD-L1 expression were associated with improved OS (p = 0.05 and p = 0.03, respectively). An inflammatory gene signature consisting of 4 genes was associated with improved ORR (p = 0.05) and OS (p = 0.01).

Conclusions: PD-1 and PD-L1 expression, biomarkers of inflammation, and inflammatory gene signatures trended with improved survival and response. While further confirmation within a larger phase III trial is needed to evaluate predictive value, these analyses indicate a role for anti-tumour immune response and treatment benefit following nivolumab treatment in HCC.

CITATION  J Hepatol . 2020 Jul 22;S0168-8278(20)30479-7.
doi: 10.1016/j.jhep.2020.07.026

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