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Phase 2 study of pembrolizumab and circulating biomarkers to predict anticancer response in advanced, unresectable hepatocellular carcinoma.
- Source :
-
Cancer [Cancer] 2019 Oct 15; Vol. 125 (20), pp. 3603-3614. Date of Electronic Publication: 2019 Jun 28. - Publication Year :
- 2019
-
Abstract
- Background: Checkpoint inhibitors have shown modest activity in patients with advanced hepatocellular carcinoma (HCC). Herein, the authors report a prospective single-institution clinical/translational phase 2 study of pembrolizumab in patients with advanced HCC and circulating biomarkers closely related to response.<br />Methods: Pembrolizumab was administered at a dose of 200 mg intravenously every 3 weeks among patients who may have developed disease progression while receiving, were intolerant of, or refused sorafenib. The circulating levels of cytokines, chemokines, programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), and PD-L2 were correlated with response, tumor PD-L1 expression, and other clinicopathological features.<br />Results: A total of 29 patients were treated and 28 patients were evaluable for response. The most common laboratory grade 3/4 adverse events were increases in aspartate aminotransferase and/or alanine aminotransferase and serum bilirubin, which for the most part were reversible. In terms of efficacy, one patient achieved a complete response and 8 patients achieved partial responses for an overall response rate of 32%. Four other patients had stable disease. The median progression-free survival was 4.5 months and the median overall survival was 13 months. Response did not correlate with prior sorafenib therapy, PD-L1 tumor staining, or a prior history of hepatitis. Correlative studies revealed that high baseline plasma TGF-β levels (≥200 pg/mL) significantly correlated with poor treatment outcomes after pembrolizumab. Tumor PD-L1 and plasma PD-L1/PD-1 levels were associated with plasma IFN-γ or IL-10.<br />Conclusions: Pembrolizumab was found to demonstrate activity in patients with advanced HCC. Toxicity generally was tolerable and reversible. A set of immunological markers in blood plasma as well as PD-L1 staining indicated that baseline TGF-β could be a predictive biomarker for response to pembrolizumab.<br /> (© 2019 American Cancer Society.)
- Subjects :
- Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized adverse effects
B7-H1 Antigen blood
Carcinoma, Hepatocellular blood
Carcinoma, Hepatocellular diagnostic imaging
Carcinoma, Hepatocellular pathology
Disease Progression
Female
Gene Expression Regulation, Neoplastic drug effects
Humans
Interferon-gamma blood
Interleukin-10 blood
Kaplan-Meier Estimate
Liver Neoplasms blood
Liver Neoplasms diagnostic imaging
Liver Neoplasms pathology
Male
Middle Aged
Programmed Cell Death 1 Receptor blood
Progression-Free Survival
Prospective Studies
Tomography, Emission-Computed
Transforming Growth Factor beta blood
Antibodies, Monoclonal, Humanized administration & dosage
Carcinoma, Hepatocellular drug therapy
Liver Neoplasms drug therapy
Treatment Outcome
Subjects
Details
- Language :
- English
- ISSN :
- 1097-0142
- Volume :
- 125
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 31251403
- Full Text :
- https://doi.org/10.1002/cncr.32339