Title |
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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Published in |
Investigational New Drugs, March 2018
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DOI | 10.1007/s10637-018-0580-2 |
Pubmed ID | |
Authors |
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 |
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/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. |
X Demographics
Geographical breakdown
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Spain | 1 | 50% |
Unknown | 1 | 50% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 50% |
Practitioners (doctors, other healthcare professionals) | 1 | 50% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 101 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Master | 10 | 10% |
Researcher | 10 | 10% |
Student > Bachelor | 10 | 10% |
Student > Ph. D. Student | 10 | 10% |
Other | 6 | 6% |
Other | 13 | 13% |
Unknown | 42 | 42% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 26 | 26% |
Biochemistry, Genetics and Molecular Biology | 16 | 16% |
Nursing and Health Professions | 5 | 5% |
Agricultural and Biological Sciences | 2 | 2% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 2% |
Other | 6 | 6% |
Unknown | 44 | 44% |