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Conference Paper: Assessment of Inflammation Biomarkers in Relation to Clinical Outcomes in Nivolumab-Treated Patients With Advanced Hepatocellular Carcinoma in CheckMate 040

TitleAssessment of Inflammation Biomarkers in Relation to Clinical Outcomes in Nivolumab-Treated Patients With Advanced Hepatocellular Carcinoma in CheckMate 040
Authors
Issue Date2019
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jhep
Citation
Annual Meeting of the American-Association-for-Cancer-Research (AACR), Atlanta, GA, 29 March - 03 April 03 2019. In Journal of Hepatology, 2019, v. 79 n. 13, suppl. S, p. abstract no. 2675 How to Cite?
AbstractIntroduction: Nivolumab (NIVO), a programmed death-1 (PD-1) inhibitor, demonstrated durable responses, manageable safety, and promising long-term survival in patients (pts) with advanced hepatocellular carcinoma (HCC), regardless of etiology, with/without prior sorafenib treatment in CheckMate 040 (El-Khoueiry, Lancet 2017). NIVO is approved in several countries for the treatment of sorafenib-experienced pts with advanced HCC. We report findings on additional exploratory biomarker analyses from NIVO-treated pts with advanced HCC from CheckMate 040. Methods: In CheckMate 040, pts with advanced HCC received NIVO monotherapy in the phase 1/2 dose-escalation (ESC; 0.1–10 mg/kg) and dose-expansion (EXP; 3 mg/kg) phases every two weeks, regardless of programmed death ligand 1 (PD-L1) status and HCC etiology. For pts in the ESC and EXP phases receiving NIVO 3 mg/kg, baseline tumor biopsy samples were analyzed using immunohistochemistry for the following markers: expression of PD-L1, PD-1, T-cell markers (CD3, CD4, CD8, FOXP3), and macrophages (CD68, CD163). Baseline tumor biopsy samples from a subset of pts in the ESC and EXP phases were evaluated using RNA sequencing to assess inflammatory signatures. Results were correlated with clinical outcomes: response (complete response [CR] + partial response [PR] vs stable disease [SD] or progressive disease [PD]) and overall survival (OS). Associations with characteristics such as etiology and geographical region (non-Asia vs Asia) were also assessed. The data cutoff date was June 2018. Results: In pts with evaluable data (n = 184), increased tumor cell PD-L1 expression was significantly associated with response (CR+PR vs SD [P = 0.00009]; CR+PR vs PD [P = 0.0007]) and OS (P = 0.03). Increased PD-1 expression was also significantly associated with response (CR+PR vs SD [P = 0.05]; CR+PR vs PD [P = 0.009]) and OS (P = 0.05). Of the T-cell markers assessed, CD3 expression was significantly associated with response (n = 182, CR+PR vs SD; P = 0.05). In pts positive for CD3 or CD8, there was a trend towards improved survival (P = 0.08). No association between CD68- and CD163-expression and clinical outcomes was observed. For the subset of pts for whom RNA sequencing data was available (n = 37), the median Bristol-Myers Squibb (BMS) inflammatory signature score was significantly higher in pts with a PR vs SD (P = 0.05) and was correlated with improved OS (P = 0.01). For all of the inflammation markers assessed, there was no association with HCC etiology or geographical region. Conclusions: In pts with advanced HCC, improved survival and response to nivolumab may be associated with higher PD-L1, PD-1 and CD3 expression, and higher BMS inflammatory signature scores. These data support the role of PD-1 inhibition in the treatment of HCC. Further investigation of these biomarkers is required.
Persistent Identifierhttp://hdl.handle.net/10722/279526
ISSN
2019 Impact Factor: 20.582
2015 SCImago Journal Rankings: 4.570
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorSangro, B-
dc.contributor.authorMelero, I-
dc.contributor.authorWadhawan, S-
dc.contributor.authorFinn, R-
dc.contributor.authorAbou-Alfa, GK-
dc.contributor.authorCheng, AL-
dc.contributor.authorYau, TCC-
dc.contributor.authorFuruse, J-
dc.contributor.authorPark, JW-
dc.contributor.authorBoyd, Z-
dc.contributor.authorTang, HT-
dc.contributor.authorShen, Y-
dc.contributor.authorTschaika, M-
dc.contributor.authorNeely, J-
dc.contributor.authorEl-Khoueiry, A-
dc.date.accessioned2019-11-01T07:19:02Z-
dc.date.available2019-11-01T07:19:02Z-
dc.date.issued2019-
dc.identifier.citationAnnual Meeting of the American-Association-for-Cancer-Research (AACR), Atlanta, GA, 29 March - 03 April 03 2019. In Journal of Hepatology, 2019, v. 79 n. 13, suppl. S, p. abstract no. 2675-
dc.identifier.issn0168-8278-
dc.identifier.urihttp://hdl.handle.net/10722/279526-
dc.description.abstractIntroduction: Nivolumab (NIVO), a programmed death-1 (PD-1) inhibitor, demonstrated durable responses, manageable safety, and promising long-term survival in patients (pts) with advanced hepatocellular carcinoma (HCC), regardless of etiology, with/without prior sorafenib treatment in CheckMate 040 (El-Khoueiry, Lancet 2017). NIVO is approved in several countries for the treatment of sorafenib-experienced pts with advanced HCC. We report findings on additional exploratory biomarker analyses from NIVO-treated pts with advanced HCC from CheckMate 040. Methods: In CheckMate 040, pts with advanced HCC received NIVO monotherapy in the phase 1/2 dose-escalation (ESC; 0.1–10 mg/kg) and dose-expansion (EXP; 3 mg/kg) phases every two weeks, regardless of programmed death ligand 1 (PD-L1) status and HCC etiology. For pts in the ESC and EXP phases receiving NIVO 3 mg/kg, baseline tumor biopsy samples were analyzed using immunohistochemistry for the following markers: expression of PD-L1, PD-1, T-cell markers (CD3, CD4, CD8, FOXP3), and macrophages (CD68, CD163). Baseline tumor biopsy samples from a subset of pts in the ESC and EXP phases were evaluated using RNA sequencing to assess inflammatory signatures. Results were correlated with clinical outcomes: response (complete response [CR] + partial response [PR] vs stable disease [SD] or progressive disease [PD]) and overall survival (OS). Associations with characteristics such as etiology and geographical region (non-Asia vs Asia) were also assessed. The data cutoff date was June 2018. Results: In pts with evaluable data (n = 184), increased tumor cell PD-L1 expression was significantly associated with response (CR+PR vs SD [P = 0.00009]; CR+PR vs PD [P = 0.0007]) and OS (P = 0.03). Increased PD-1 expression was also significantly associated with response (CR+PR vs SD [P = 0.05]; CR+PR vs PD [P = 0.009]) and OS (P = 0.05). Of the T-cell markers assessed, CD3 expression was significantly associated with response (n = 182, CR+PR vs SD; P = 0.05). In pts positive for CD3 or CD8, there was a trend towards improved survival (P = 0.08). No association between CD68- and CD163-expression and clinical outcomes was observed. For the subset of pts for whom RNA sequencing data was available (n = 37), the median Bristol-Myers Squibb (BMS) inflammatory signature score was significantly higher in pts with a PR vs SD (P = 0.05) and was correlated with improved OS (P = 0.01). For all of the inflammation markers assessed, there was no association with HCC etiology or geographical region. Conclusions: In pts with advanced HCC, improved survival and response to nivolumab may be associated with higher PD-L1, PD-1 and CD3 expression, and higher BMS inflammatory signature scores. These data support the role of PD-1 inhibition in the treatment of HCC. Further investigation of these biomarkers is required.-
dc.languageeng-
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jhep-
dc.relation.ispartofJournal of Hepatology-
dc.titleAssessment of Inflammation Biomarkers in Relation to Clinical Outcomes in Nivolumab-Treated Patients With Advanced Hepatocellular Carcinoma in CheckMate 040-
dc.typeConference_Paper-
dc.identifier.emailYau, TCC: tyaucc@hku.hk-
dc.identifier.authorityYau, TCC=rp01466-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1158/1538-7445.AM2019-2675-
dc.identifier.hkuros308521-
dc.identifier.volume79-
dc.identifier.issue13, suppl. S-
dc.identifier.spageabstract no. 2675-
dc.identifier.epageabstract no. 2675-
dc.identifier.isiWOS:000488279401125-
dc.publisher.placeNetherlands-

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