https://scholars.lib.ntu.edu.tw/handle/123456789/580017
標題: | Association of inflammatory biomarkers with clinical outcomes in nivolumab-treated patients with advanced hepatocellular carcinoma | 作者: | Sangro B. Melero I. Wadhawan S. Finn R.S. Abou-Alfa G.K. ANN-LII CHENG Yau T. Furuse J. Park J.-W. Boyd Z. Tang H.T. Shen Y. Tschaika M. Neely J. El-Khoueiry A. |
關鍵字: | Hepatocellular carcinoma; Inflammatory gene expression signatures; Ipilimumab; Nivolumab; Programmed death ligand 1 (PD-L1) | 公開日期: | 2020 | 出版社: | Elsevier B.V. | 卷: | 73 | 期: | 6 | 起(迄)頁: | 1460-1469 | 來源出版物: | Journal of Hepatology | 摘要: | Background & Aims: Nivolumab, a programmed death (PD)-1 (PD-1) inhibitor, led to durable responses, manageable safety, and increased survival in patients with advanced hepatocellular carcinoma (HCC). In our retrospective analysis, we studied the immunobiology and potential associations between biomarkers and outcomes with nivolumab in HCC. Methods: Fresh and archival tumour samples from dose-escalation and dose-expansion phases of the CheckMate 040 trial were analysed by immunohistochemistry and RNA sequencing to assess several inflammatory gene expression signatures, including CD274 (PD-ligand 1 [PD-L1]), CD8A, LAG3, and STAT1. Biomarkers were assessed for association with clinical outcomes (best overall response by blinded independent central review per RECIST v1.1 and overall survival [OS]). Results: Complete or partial tumour responses were observed in PD-L1–positive and PD-L1–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 objective response rate (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 of these biomarkers, these exploratory analyses suggest that anti-tumour immune response may play a role in the treatment benefit of nivolumab in HCC. Lay summary: Certain tests may be used to provide a picture of how a tumour is escaping the immune system, allowing it to continue to grow and create more tumours. Therapies such as nivolumab are designed to help the immune system fight the tumour. These tests may be used to determine how effective such therapies will be in the treatment of advanced liver cancer. NCT number: NCT01658878. ? 2020 European Association for the Study of the Liver |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85092009560&doi=10.1016%2fj.jhep.2020.07.026&partnerID=40&md5=beaed0fe8e37a45bb64d3d72b44dfa05 https://scholars.lib.ntu.edu.tw/handle/123456789/580017 |
ISSN: | 0168-8278 | DOI: | 10.1016/j.jhep.2020.07.026 | SDG/關鍵字: | biological marker; CD3 antigen; CD8 antigen; CD8alpha antigen; nivolumab; programmed death 1 ligand 1; STAT1 protein; CD223 antigen; CD8 antigen; CD8 antigen, alpha chain; ipilimumab; leukocyte antigen; nivolumab; pharmacological biomarker; programmed death 1 ligand 1; programmed death 1 receptor; STAT1 protein; STAT1 protein, human; tumor marker; adult; advanced cancer; Article; cancer patient; clinical outcome; clinical trial; controlled study; deterioration; drug dose escalation; female; gene; gene expression; human; human cell; human tissue; immune response; immunobiology; immunohistochemistry; lag3 gene; liver cell carcinoma; macrophage; male; overall survival; phase 3 clinical trial; priority journal; retrospective study; RNA sequencing; virus load; administration and dosage; adverse event; drug monitoring; immunology; liver tumor; middle aged; mortality; multicenter study; pathology; phase 1 clinical trial; phase 2 clinical trial; procedures; survival analysis; Antigens, CD; B7-H1 Antigen; Biomarkers, Pharmacological; Biomarkers, Tumor; Carcinoma, Hepatocellular; CD8 Antigens; Drug Monitoring; Female; Humans; Immune Checkpoint Inhibitors; Immunohistochemistry; Ipilimumab; Liver Neoplasms; Male; Middle Aged; Nivolumab; Programmed Cell Death 1 Receptor; STAT1 Transcription Factor; Survival Analysis |
顯示於: | 醫學系 |
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