Ruxolitinib + capecitabine in advanced/metastatic pancreatic cancer after disease progression/intolerance to first-line therapy: JANUS 1 and 2 randomized phase III studies

Herbert Hurwitz, Eric Van Cutsem, Johanna Bendell, Manuel Hidalgo, Chung Pin Li, Marcelo Garrido Salvo, Teresa Macarulla, Vaibhav Sahai, Ashwin Sama, Edward W Greeno, Kenneth H. Yu, Chris Verslype, Fitzroy Dawkins, Chris Walker, Jason Clark, Eileen M. O’Reilly

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Background Ruxolitinib, a Janus kinase 1 (JAK1)/JAK2 inhibitor, plus capecitabine improved overall survival (OS) vs capecitabine in a subgroup analysis of patients with metastatic pancreatic cancer and systemic inflammation (C-reactive protein [CRP] >13 mg/dL) in the randomized phase II RECAP study. We report results from two randomized phase III studies, JANUS 1 (NCT02117479) and JANUS 2 (NCT02119663). Patients and Methods Adults with advanced/metastatic pancreatic cancer, one prior chemotherapy regimen and CRP >10 mg/L were randomized 1:1 (stratified by modified Glasgow Prognostic Score [1 vs 2] and Eastern Cooperative Oncology Group performance status [0/1 vs 2]) to 21-day cycles of ruxolitinib 15 mg twice daily plus capecitabine 2000 mg/m 2 /day (Days 1–14) or placebo plus capecitabine. The primary endpoint was OS. Results Both studies were terminated following a planned interim futility/efficacy analysis of JANUS 1. Overall, 321 and 86 patients were randomized in JANUS 1 (ruxolitinib: n = 161; placebo: n = 160) and JANUS 2 (ruxolitinib: n = 43; placebo: n = 43). There was no significant difference in OS or progression-free survival (PFS) between treatments in JANUS 1 (OS: hazard ratio [HR], 0.969, 95% confidence interval [CI], 0.747–1.256; PFS: HR, 1.056; 95% CI, 0.827–1.348) or JANUS 2 (OS: HR, 1.584; 95% CI, 0.886–2.830; PFS: HR, 1.166; 95% CI, 0.687–1.978). The most common hematologic adverse event was anemia. No new safety signals with ruxolitinib or capecitabine were identified. Conclusions Ruxolitinib plus capecitabine was well tolerated in refractory pancreatic cancer patients; this combination did not improve survival.

Original languageEnglish (US)
Pages (from-to)683-695
Number of pages13
JournalInvestigational New Drugs
Volume36
Issue number4
DOIs
StatePublished - Aug 1 2018

Bibliographical note

Funding Information:
Acknowledgments The authors wish to thank the patients and their families, the investigators, and the site personnel who participated in this study. This study was sponsored by Incyte Corporation (Wilmington, DE, USA). Medical writing assistance was provided by Sneha D’Silva, MD, on behalf of Evidence Scientific Solutions Inc. (Philadelphia, PA, USA), and funded by Incyte.

Funding Information:
Funding This study was sponsored by Incyte Corporation (Wilmington, DE, USA).

Publisher Copyright:
© 2018, Springer Science+Business Media, LLC, part of Springer Nature.

Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.

Keywords

  • Clinical trial
  • JAK1 protein tyrosine kinase
  • JAK2 protein tyrosine kinase
  • Pancreatic neoplasms

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