Skip to main content
construction release_alert
Scholars@Duke will be undergoing maintenance April 11-15. Some features may be unavailable during this time.
cancel

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.

Publication ,  Journal Article
Hurwitz, HI; Uppal, N; Wagner, SA; Bendell, JC; Beck, JT; Wade, SM; Nemunaitis, JJ; Stella, PJ; Pipas, JM; Wainberg, ZA; Manges, R; Hunter, DS ...
Published in: J Clin Oncol
December 1, 2015

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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

December 1, 2015

Volume

33

Issue

34

Start / End Page

4039 / 4047

Location

United States

Related Subject Headings

  • Survival Rate
  • Pyrimidines
  • Pyrazoles
  • Prognosis
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis
  • Nitriles
  • Neoplasm Staging
  • Middle Aged
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Hurwitz, H. I., Uppal, N., Wagner, S. A., Bendell, J. C., Beck, J. T., Wade, S. M., … Levy, R. S. (2015). 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, 33(34), 4039–4047. https://doi.org/10.1200/JCO.2015.61.4578
Hurwitz, Herbert I., Nikhil Uppal, Stephanie A. Wagner, Johanna C. Bendell, J Thaddeus Beck, Seaborn M. Wade, John J. Nemunaitis, et al. “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 33, no. 34 (December 1, 2015): 4039–47. https://doi.org/10.1200/JCO.2015.61.4578.
Hurwitz, Herbert I., et al. “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, vol. 33, no. 34, Dec. 2015, pp. 4039–47. Pubmed, doi:10.1200/JCO.2015.61.4578.
Hurwitz HI, Uppal N, Wagner SA, Bendell JC, Beck JT, Wade SM, Nemunaitis JJ, Stella PJ, Pipas JM, Wainberg ZA, Manges R, Garrett WM, Hunter DS, Clark J, Leopold L, Sandor V, Levy RS. 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):4039–4047.

Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

December 1, 2015

Volume

33

Issue

34

Start / End Page

4039 / 4047

Location

United States

Related Subject Headings

  • Survival Rate
  • Pyrimidines
  • Pyrazoles
  • Prognosis
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis
  • Nitriles
  • Neoplasm Staging
  • Middle Aged
  • Male