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

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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.

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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

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

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Authors and Affiliations

  1. Duke University Medical Center, Campus mail 439 Seeley-mudd Bldg, 10 Bryan Searle Drive, Duke University M, Durham, NC, 27710, USA

    Herbert Hurwitz

  2. Clinical Digestive Oncology, University Hospitals Leuven and KU Leuven, UZ Herestraat 49, 3000, Leuven, Belgium

    Eric Van Cutsem & Chris Verslype

  3. Sarah Cannon Research Institute/Tennessee Oncology, 250 25th Ave N, Nashville, TN, 37203, USA

    Johanna Bendell

  4. Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA, 02215, USA

    Manuel Hidalgo

  5. Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Road, Beitou District, Taipei, 11217, Taiwan

    Chung-Pin Li

  6. School of Medicine, National Yang-Ming University, No. 155, Sec. 2, Li-Nong Street, Beitou District, Taipei, 112, Taiwan

    Chung-Pin Li

  7. Pontificia Universidad Católica de Chile, Av Libertador Bernardo O’Higgins, 340, Santiago, Región Metropolitana, Chile

    Marcelo Garrido Salvo

  8. Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron University Hospital (HUVH), Passeig de la Vall d’Hebron, 119-129, 08035, Barcelona, Spain

    Teresa Macarulla

  9. Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan, Cancer Center Floor B1 Reception E, 1500 E Medical Center Dr SPC 5912, Ann Arbor, MI, 48109-5912, USA

    Vaibhav Sahai

  10. Thomas Jefferson University Hospital, 925 Chestnut Street, Suite 320A, Philadelphia, PA, 19107, USA

    Ashwin Sama

  11. Division of Hematology, Oncology and Transplantation, University of Minnesota, 420 Delaware Street SE, MMC 480, Minneapolis, MN, 55455, USA

    Edward Greeno

  12. Memorial Sloan Kettering Cancer Center, 300 East 66th Street, New York, NY, 10065, USA

    Kenneth H. Yu & Eileen M. O’Reilly

  13. Incyte Corporation, 1801 Augustine Cut-off, Wilmington, DE, 19803, USA

    Fitzroy Dawkins, Chris Walker & Jason Clark

  14. Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA

    Eileen M. O’Reilly

Authors
  1. Herbert Hurwitz
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  2. Eric Van Cutsem
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  6. Marcelo Garrido Salvo
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  7. Teresa Macarulla
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  16. Eileen M. O’Reilly
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Contributions

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.

Corresponding author

Correspondence to Eileen M. O’Reilly.

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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.

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

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Hurwitz, H., Van Cutsem, E., Bendell, J. et al. Ruxolitinib + capecitabine in advanced/metastatic pancreatic cancer after disease progression/intolerance to first-line therapy: JANUS 1 and 2 randomized phase III studies. Invest New Drugs 36, 683–695 (2018). https://doi.org/10.1007/s10637-018-0580-2

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