Randomized, Double-Blind, Phase II Study of Ruxolitinib or Placebo in Combination With Capecitabine in Patients With Metastatic Pancreatic Cancer for Whom Therapy With Gemcitabine Has Failed.

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 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.

• Authors: Herbert I Hurwitz, Nikhil Uppal, Stephanie A Wagner, Johanna C Bendell, J Thaddeus Beck, Seaborn M Wade 3rd, John J Nemunaitis, Philip J Stella, J Marc Pipas, Zev A Wainberg, Robert Manges, William M Garrett, Deborah S Hunter, Jason Clark, Lance Leopold, Victor Sandor, Richard S Levy
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 33 Issue 34 Pg. 4039-47 (Dec 01 2015) ISSN: 1527-7755 [Electronic] United States
• PMID: 26351344 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by American Society of Clinical Oncology.

Chemical References

• Nitriles
• Pyrazoles
• Pyrimidines
• Deoxycytidine
• Capecitabine
• ruxolitinib
• Gemcitabine

Topics

• Adenocarcinoma (drug therapy, mortality, secondary)
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Capecitabine (administration & dosage)
• Cohort Studies
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Double-Blind Method
• Female
• Follow-Up Studies
• Humans
• Liver Neoplasms (drug therapy, mortality, secondary)
• Lung Neoplasms (drug therapy, mortality, secondary)
• Lymphatic Metastasis
• Male
• Middle Aged
• Neoplasm Staging
• Nitriles
• Pancreatic Neoplasms (drug therapy, mortality, pathology)
• Prognosis
• Pyrazoles (administration & dosage)
• Pyrimidines
• Survival Rate
• Gemcitabine