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

J Clin Oncol. 2015 Dec 1;33(34):4039-47. doi: 10.1200/JCO.2015.61.4578. Epub 2015 Sep 8.

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.

Trial registration: ClinicalTrials.gov NCT01423604.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Nitriles
  • Pyrazoles
  • Pyrimidines
  • Deoxycytidine
  • Capecitabine
  • ruxolitinib
  • gemcitabine

Associated data

  • ClinicalTrials.gov/NCT01423604