Herbert I Hurwitz1, Nikhil Uppal2, Stephanie A Wagner2, Johanna C Bendell2, J Thaddeus Beck2, Seaborn M Wade2, John J Nemunaitis2, Philip J Stella2, J Marc Pipas2, Zev A Wainberg2, Robert Manges2, William M Garrett2, Deborah S Hunter2, Jason Clark2, Lance Leopold2, Victor Sandor2, Richard S Levy2. 1. Herbert I. Hurwitz, Duke University Medical Center, Durham, NC; Nikhil Uppal, New York University Langone Arena Oncology, Lake Success, NY; Stephanie A. Wagner, Indiana University Melvin and Bren Simon Cancer Center; Robert Manges, Investigative Clinical Research of Indiana, Indianapolis, IN; Johanna C. Bendell, Sarah Cannon Research Institute, Nashville, TN; J. Thaddeus Beck, Highlands Oncology Group, Fayetteville, AR; Seaborn M. Wade III, Virginia Cancer Institute, Richmond, VA; John J. Nemunaitis, Mary Crowley Medical Research Center, Dallas, TX; Philip J. Stella, St Joseph Mercy Health System, Alexander Cancer Care Center, Ann Arbor, MI; J. Marc Pipas, Dartmouth Hitchcock Medical Center/Norris Cotton Cancer Center, Lebanon, NH; Zev A. Wainberg, University of California, Los Angeles, Los Angeles, CA; and William M. Garrett, Deborah S. Hunter, Jason Clark, Lance Leopold, Victor Sandor, and Richard S. Levy, Incyte Corporation, Wilmington, DE. herbert.hurwitz@duke.edu. 2. Herbert I. Hurwitz, Duke University Medical Center, Durham, NC; Nikhil Uppal, New York University Langone Arena Oncology, Lake Success, NY; Stephanie A. Wagner, Indiana University Melvin and Bren Simon Cancer Center; Robert Manges, Investigative Clinical Research of Indiana, Indianapolis, IN; Johanna C. Bendell, Sarah Cannon Research Institute, Nashville, TN; J. Thaddeus Beck, Highlands Oncology Group, Fayetteville, AR; Seaborn M. Wade III, Virginia Cancer Institute, Richmond, VA; John J. Nemunaitis, Mary Crowley Medical Research Center, Dallas, TX; Philip J. Stella, St Joseph Mercy Health System, Alexander Cancer Care Center, Ann Arbor, MI; J. Marc Pipas, Dartmouth Hitchcock Medical Center/Norris Cotton Cancer Center, Lebanon, NH; Zev A. Wainberg, University of California, Los Angeles, Los Angeles, CA; and William M. Garrett, Deborah S. Hunter, Jason Clark, Lance Leopold, Victor Sandor, and Richard S. Levy, Incyte Corporation, Wilmington, DE.
Abstract
PURPOSE:Patients with advanced pancreatic adenocarcinoma have a poor prognosis and limited second-line treatment options. Evidence suggests a role for the Janus kinase (JAK)/signal transducer and activator of transcription pathway in the pathogenesis and clinical course of pancreatic cancer. PATIENTS AND METHODS: In this double-blind, phase II study, patients with metastatic pancreatic cancer who had experienced treatment failure withgemcitabine were randomly assigned 1:1 to the JAK1/JAK2 inhibitor ruxolitinib (15 mg twice daily) plus capecitabine (1,000 mg/m(2) twice daily) or placebo plus capecitabine. The primary end point was overall survival (OS); secondary end points included progression-free survival, clinical benefit response, objective response rate, and safety. Prespecified subgroup analyses evaluated treatment heterogeneity and efficacy in patients with evidence of inflammation. RESULTS: In the intent-to-treat population (ruxolitinib, n = 64; placebo, n = 63), the hazard ratio was 0.79 (95% CI, 0.53 to 1.18; P = .25) for OS and was 0.75 (95% CI, 0.52 to 1.10; P = .14) for progression-free survival. In a prespecified subgroup analysis of patients with inflammation, defined by serum C-reactive protein levels greater than the study population median (ie, 13 mg/L), OS was significantly greater with ruxolitinib than with placebo (hazard ratio, 0.47; 95% CI, 0.26 to 0.85; P = .011). Prolonged survival in this subgroup was supported by post hoc analyses of OS that categorized patients by the modified Glasgow Prognostic Score, a systemic inflammation-based prognostic system. Grade 3 or greater adverse events were observed with similar frequency in the ruxolitinib (74.6%) and placebo (81.7%) groups. Grade 3 or greater anemia was more frequent with ruxolitinib (15.3%; placebo, 1.7%). CONCLUSION:Ruxolitinib plus capecitabine was generally well tolerated and may improve survival in patients with metastatic pancreatic cancer and evidence of systemic inflammation.
RCT Entities:
PURPOSE:Patients with advanced pancreatic adenocarcinoma have a poor prognosis and limited second-line treatment options. Evidence suggests a role for the Janus kinase (JAK)/signal transducer and activator of transcription pathway in the pathogenesis and clinical course of pancreatic cancer. PATIENTS AND METHODS: In this double-blind, phase II study, patients with metastatic pancreatic cancer who had experienced treatment failure with gemcitabine were randomly assigned 1:1 to the JAK1/JAK2 inhibitor ruxolitinib (15 mg twice daily) plus capecitabine (1,000 mg/m(2) twice daily) or placebo plus capecitabine. The primary end point was overall survival (OS); secondary end points included progression-free survival, clinical benefit response, objective response rate, and safety. Prespecified subgroup analyses evaluated treatment heterogeneity and efficacy in patients with evidence of inflammation. RESULTS: In the intent-to-treat population (ruxolitinib, n = 64; placebo, n = 63), the hazard ratio was 0.79 (95% CI, 0.53 to 1.18; P = .25) for OS and was 0.75 (95% CI, 0.52 to 1.10; P = .14) for progression-free survival. In a prespecified subgroup analysis of patients with inflammation, defined by serum C-reactive protein levels greater than the study population median (ie, 13 mg/L), OS was significantly greater with ruxolitinib than with placebo (hazard ratio, 0.47; 95% CI, 0.26 to 0.85; P = .011). Prolonged survival in this subgroup was supported by post hoc analyses of OS that categorized patients by the modified Glasgow Prognostic Score, a systemic inflammation-based prognostic system. Grade 3 or greater adverse events were observed with similar frequency in the ruxolitinib (74.6%) and placebo (81.7%) groups. Grade 3 or greater anemia was more frequent with ruxolitinib (15.3%; placebo, 1.7%). CONCLUSION:Ruxolitinib plus capecitabine was generally well tolerated and may improve survival in patients with metastatic pancreatic cancer and evidence of systemic inflammation.
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