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

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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

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Pancreatic Neoplasms
Disease Progression
Survival
Confidence Intervals
Disease-Free Survival
Placebos
C-Reactive Protein
Janus Kinase 1
Therapeutics
Medical Futility
Capecitabine
INCB018424
Anemia
Inflammation
Safety
Drug Therapy

Keywords

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

Cite this

Ruxolitinib + capecitabine in advanced/metastatic pancreatic cancer after disease progression/intolerance to first-line therapy : JANUS 1 and 2 randomized phase III studies. / Hurwitz, Herbert; Van Cutsem, Eric; Bendell, Johanna; Hidalgo, Manuel; Li, Chung Pin; Salvo, Marcelo Garrido; Macarulla, Teresa; Sahai, Vaibhav; Sama, Ashwin; Greeno, Edward W; Yu, Kenneth H.; Verslype, Chris; Dawkins, Fitzroy; Walker, Chris; Clark, Jason; O’Reilly, Eileen M.

In: Investigational New Drugs, Vol. 36, No. 4, 01.08.2018, p. 683-695.

Research output: Contribution to journalArticle

Hurwitz, H, Van Cutsem, E, Bendell, J, Hidalgo, M, Li, CP, Salvo, MG, Macarulla, T, Sahai, V, Sama, A, Greeno, EW, Yu, KH, Verslype, C, Dawkins, F, Walker, C, Clark, J & O’Reilly, EM 2018, 'Ruxolitinib + capecitabine in advanced/metastatic pancreatic cancer after disease progression/intolerance to first-line therapy: JANUS 1 and 2 randomized phase III studies', Investigational New Drugs, vol. 36, no. 4, pp. 683-695. https://doi.org/10.1007/s10637-018-0580-2
Hurwitz, Herbert ; Van Cutsem, Eric ; Bendell, Johanna ; Hidalgo, Manuel ; Li, Chung Pin ; Salvo, Marcelo Garrido ; Macarulla, Teresa ; Sahai, Vaibhav ; Sama, Ashwin ; Greeno, Edward W ; Yu, Kenneth H. ; Verslype, Chris ; Dawkins, Fitzroy ; Walker, Chris ; Clark, Jason ; O’Reilly, Eileen M. / Ruxolitinib + capecitabine in advanced/metastatic pancreatic cancer after disease progression/intolerance to first-line therapy : JANUS 1 and 2 randomized phase III studies. In: Investigational New Drugs. 2018 ; Vol. 36, No. 4. pp. 683-695.
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title = "Ruxolitinib + capecitabine in advanced/metastatic pancreatic cancer after disease progression/intolerance to first-line therapy: JANUS 1 and 2 randomized phase III studies",
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.",
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author = "Herbert Hurwitz and {Van Cutsem}, Eric and Johanna Bendell and Manuel Hidalgo and Li, {Chung Pin} and Salvo, {Marcelo Garrido} and Teresa Macarulla and Vaibhav Sahai and Ashwin Sama and Greeno, {Edward W} and Yu, {Kenneth H.} and Chris Verslype and Fitzroy Dawkins and Chris Walker and Jason Clark and O’Reilly, {Eileen M.}",
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T1 - Ruxolitinib + capecitabine in advanced/metastatic pancreatic cancer after disease progression/intolerance to first-line therapy

T2 - JANUS 1 and 2 randomized phase III studies

AU - Hurwitz, Herbert

AU - Van Cutsem, Eric

AU - Bendell, Johanna

AU - Hidalgo, Manuel

AU - Li, Chung Pin

AU - Salvo, Marcelo Garrido

AU - Macarulla, Teresa

AU - Sahai, Vaibhav

AU - Sama, Ashwin

AU - Greeno, Edward W

AU - Yu, Kenneth H.

AU - Verslype, Chris

AU - Dawkins, Fitzroy

AU - Walker, Chris

AU - Clark, Jason

AU - O’Reilly, Eileen M.

PY - 2018/8/1

Y1 - 2018/8/1

N2 - 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.

AB - 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.

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KW - JAK1 protein tyrosine kinase

KW - JAK2 protein tyrosine kinase

KW - Pancreatic neoplasms

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