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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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.
KeywordsClinical trial JAK1 protein tyrosine kinase JAK2 protein tyrosine kinase Pancreatic neoplasms
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.
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.
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.
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 was obtained from all individual participants included in the study.
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