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Investigational New Drugs

, Volume 36, Issue 4, pp 683–695 | Cite as

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 Greeno
  • Kenneth H. Yu
  • Chris Verslype
  • Fitzroy Dawkins
  • Chris Walker
  • Jason Clark
  • Eileen M. O’Reilly
PHASE III STUDIES

Summary

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/m2/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.

Keywords

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

Notes

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.

Author contribution

Conception/design of the work: Hurwitz, Van Cutsem, Bendell, Hidalgo, Li, Garrido, Macarulla, Sahai, Sama, Greeno, Yu, Verslype, Clark, O’Reilly.

Acquisition of data: Hurwitz, Van Cutsem, Bendell, Hidalgo, Li, Garrido, Macarulla, Sahai, Sama, Greeno, Yu, Verslype, O’Reilly.

Data analysis and interpretation: Dawkins, Walker, Clark.

Writing, review, and revision of the manuscript: All authors.

Final approval of the manuscript: All authors.

Funding

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

Compliance with ethical standards

Conflicts of interest

Hurwitz: Honoraria – Genentech/Roche, Lilly/ImClone; Consulting or advisory role – Acceleron Pharma, Bristol-Myers Squibb, Genentech/Roche, GlaxoSmithKline, Incyte, Lilly, Novartis, OncoMed, TRACON Pharma; Research funding – Bristol-Myers Squibb (Inst), Genentech/Roche (Inst), GlaxoSmithKline (Inst), Lilly (Inst), Macrogenics (Inst), NCI (Inst), Novartis (Inst), Regeneron (Inst), TRACON Pharma (Inst); Employment – Genentech/Roche as of 23 October 2017. Van Cutsem: Research funding – Amgen (Inst), Bayer (Inst), Boehringer Ingelheim (Inst), Celgene (Inst), Ipsen (Inst), Lilly (Inst), Merck Serono (Inst), Novartis (Inst), Roche (Inst), Sanofi (Inst). Bendell: Research funding – Incyte. Sahai: Consulting – Celgene, Halozyme, NewLink; Research funding – Agios (Inst), Bristol-Myers Squibb (Inst), Celgene (Inst), Incyte (Inst). Sama: Honoraria – OncoPlex Diagnostics; Research funding – Bristol-Myers Squibb (Inst), Incyte (Inst), MedImmune (Inst), OncoMed (Inst), Precision Biologics (Inst); Employment – Bristol-Myers Squibb (Inst) as of March 20, 2017. Yu: Consulting or advisory role – Celgene, Merck Serono, Merrimack. Dawkins, Walker, Clark: Employment – Incyte; Stock and other ownership interests – Incyte. O’Reilly: Consulting or advisory role – Aduro Biotech, Astellas Pharma (Inst), Celgene, Celsion (Inst), Cipla, Exelixis (Inst), Gilead Sciences, Hexal (Inst), IntegraGen (Inst), Jennerex (Inst), Lilly (Inst), MedImmune, Merrimack, Novartis (Inst), Pharmacyclics, Sanofi, Silenseed, Vicus Therapeutics; Research funding – AstraZeneca/MedImmune (Inst), Bristol-Myers Squibb (Inst), Celgene (Inst), Immunomedics (Inst), Incyte (Inst), Momenta Pharmaceuticals (Inst), Myriad Genetics (Inst), OncoMed (Inst), Polaris (Inst), Sanofi (Inst). Hidalgo, Li, Garrido, Macarulla, Greeno, Verslype: Nothing to disclose.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Herbert Hurwitz
    • 1
  • Eric Van Cutsem
    • 2
  • Johanna Bendell
    • 3
  • Manuel Hidalgo
    • 4
  • Chung-Pin Li
    • 5
    • 6
  • Marcelo Garrido Salvo
    • 7
  • Teresa Macarulla
    • 8
  • Vaibhav Sahai
    • 9
  • Ashwin Sama
    • 10
  • Edward Greeno
    • 11
  • Kenneth H. Yu
    • 12
  • Chris Verslype
    • 2
  • Fitzroy Dawkins
    • 13
  • Chris Walker
    • 13
  • Jason Clark
    • 13
  • Eileen M. O’Reilly
    • 12
    • 14
  1. 1.Duke University Medical CenterDurhamUSA
  2. 2.Clinical Digestive OncologyUniversity Hospitals Leuven and KU LeuvenLeuvenBelgium
  3. 3.Sarah Cannon Research Institute/Tennessee OncologyNashvilleUSA
  4. 4.Beth Israel Deaconess Medical CenterBostonUSA
  5. 5.Division of Gastroenterology and Hepatology, Department of MedicineTaipei Veterans General HospitalTaipeiTaiwan
  6. 6.School of MedicineNational Yang-Ming UniversityTaipeiTaiwan
  7. 7.Pontificia Universidad Católica de ChileSantiagoChile
  8. 8.Vall d’Hebron Institute of Oncology (VHIO)Vall d’Hebron University Hospital (HUVH)BarcelonaSpain
  9. 9.Division of Hematology and Oncology, Department of Internal MedicineUniversity of MichiganAnn ArborUSA
  10. 10.Thomas Jefferson University HospitalPhiladelphiaUSA
  11. 11.Division of Hematology, Oncology and TransplantationUniversity of MinnesotaMinneapolisUSA
  12. 12.Memorial Sloan Kettering Cancer CenterNew YorkUSA
  13. 13.Incyte CorporationWilmingtonUSA
  14. 14.Weill Cornell Medical CollegeNew YorkUSA

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