Lynn G Feun1,2, Ying-Ying Li2, Chunjing Wu3, Medhi Wangpaichitr4, Patricia D Jones1,2, Stephen P Richman1,2, Beatrice Madrazo5, Deukwoo Kwon6, Monica Garcia-Buitrago7, Paul Martin2, Peter J Hosein2, Niramol Savaraj2,3. 1. Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida. 2. Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida. 3. Division of Hematology and Oncology, Miami Veterans Affairs Healthcare System, Miami, Florida. 4. Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida. 5. Department of Radiology, University of Miami Miller School of Medicine, Miami, Florida. 6. Biostatistics and Bioinformatics Shared Resource, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida. 7. Department of Pathology, University of Miami Miller School of Medicine, Miami, Florida.
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. 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. 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. 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.
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. 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. 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. 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.
Authors: Ioannis A Ziogas; Alexandros P Evangeliou; Lipika Goyal; Georgios Tsoulfas; Dimitrios Giannis; Muhammad H Hayat; Konstantinos S Mylonas; Samer Tohme; David A Geller; Nahel Elias Journal: Oncologist Date: 2021-01-02
Authors: Cameron J Herting; Matthew R Farren; Yan Tong; Ziyue Liu; Bert O'Neil; Tanios Bekaii-Saab; Anne Noonan; Christopher McQuinn; Thomas A Mace; Walid Shaib; Christina Wu; Bassel F El-Rayes; Safi Shahda; Gregory B Lesinski Journal: Cancer Immunol Immunother Date: 2021-06-23 Impact factor: 6.968