A phase II and biomarker study of ramucirumab, a human monoclonal antibody targeting the VEGF receptor-2, as first-line monotherapy in patients with advanced hepatocellular cancer.

Clin Cancer Res

Authors' Affiliations: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; David Geffen School of Medicine, University of California, Los Angeles, California; Northwestern University Feinberg School of Medicine, Chicago Illinois; East Jefferson General Hospital, Metairie, Louisiana; Division of Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; ImClone Systems, a wholly-owned subsidiary of Eli Lilly and company, Bridgewater, New Jersey; Eli Lilly and Company, Indianapolis, Indiana; and Lahey Hospital and Medical Center, Tufts University School of Medicine, Burlington, Massachusetts.

Published: December 2013

Purpose: To assess the efficacy and safety of the anti-VEGF receptor-2 (VEGFR-2) antibody ramucirumab as first-line therapy in patients with advanced hepatocellular carcinoma and explore potential circulating biomarkers.

Experimental Design: Adults with advanced hepatocellular carcinoma and no prior systemic treatment received ramucirumab 8 mg/kg every two weeks until disease progression or limiting toxicity. The primary endpoint was progression-free survival (PFS); secondary endpoints included objective response rate (ORR) and overall survival (OS). Circulating biomarkers were evaluated before and after ramucirumab treatment in a subset of patients.

Results: Forty-two patients received ramucirumab. Median PFS was 4.0 months [95% confidence interval (CI), 2.6-5.7], ORR was 9.5% (95% CI, 2.7-22.6; 4/42 patients had a partial response), and median OS was 12.0 months (95% CI, 6.1-19.7). For patients with Barcelona Clinic Liver Cancer (BCLC) stage C disease, median OS was 4.4 months (95% CI, 0.5-9.0) for patients with Child-Pugh B cirrhosis versus 18.0 months (95% CI, 6.1-23.5) for patients with Child-Pugh A cirrhosis. Treatment-related grade ≥ 3 toxicities included hypertension (14%), gastrointestinal hemorrhage and infusion-related reactions (7% each), and fatigue (5%). There was one treatment-related death (gastrointestinal hemorrhage). After treatment with ramucirumab, there was an increase in serum VEGF and placental growth factor (PlGF) and a transient decrease in soluble VEGFR-2.

Conclusion: Ramucirumab monotherapy may confer anticancer activity in advanced hepatocellular carcinoma with an acceptable safety profile. Exploratory biomarker studies showed changes in circulating VEGF, PlGF, and sVEGFR-2 that are consistent with those seen with other anti-VEGF agents.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4795808PMC
http://dx.doi.org/10.1158/1078-0432.CCR-13-1442DOI Listing

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