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

doi:10.1007/s10637-018-0580-2

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

Medicine - Hematology, Oncology, Transplant

Research output: Contribution to journal › Article › peer-review

73 Scopus citations

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 language	English (US)
Pages (from-to)	683-695
Number of pages	13
Journal	Investigational New Drugs
Volume	36
Issue number	4
DOIs	https://doi.org/10.1007/s10637-018-0580-2
State	Published - Aug 1 2018

Bibliographical note

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

Funding Information:
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.

Publisher Copyright:
© 2018, Springer Science+Business Media, LLC, part of Springer Nature.

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s10637-018-0580-2

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752723

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Hurwitz, H., Van Cutsem, E., Bendell, J., Hidalgo, M., Li, C. P., Salvo, M. G., Macarulla, T., Sahai, V., Sama, A., Greeno, E. W., Yu, K. H., Verslype, C., Dawkins, F., Walker, C., Clark, J., & O’Reilly, E. M. (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, 36(4), 683-695. https://doi.org/10.1007/s10637-018-0580-2

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

Research output: Contribution to journal › Article › peer-review

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

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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.",

keywords = "Clinical trial, JAK1 protein tyrosine kinase, JAK2 protein tyrosine kinase, Pancreatic neoplasms",

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{\textquoteright}Reilly, {Eileen M.}",

note = "Funding Information: Funding This study was sponsored by Incyte Corporation (Wilmington, DE, USA). Funding Information: 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{\textquoteright}Silva, MD, on behalf of Evidence Scientific Solutions Inc. (Philadelphia, PA, USA), and funded by Incyte. Publisher Copyright: {\textcopyright} 2018, Springer Science+Business Media, LLC, part of Springer Nature.",

year = "2018",

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doi = "10.1007/s10637-018-0580-2",

language = "English (US)",

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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.

N1 - Funding Information: Funding This study was sponsored by Incyte Corporation (Wilmington, DE, USA). Funding Information: 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. Publisher Copyright: © 2018, Springer Science+Business Media, LLC, part of Springer Nature.

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.

KW - Clinical trial

KW - JAK1 protein tyrosine kinase

KW - JAK2 protein tyrosine kinase

KW - Pancreatic neoplasms

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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

Abstract

Bibliographical note

Keywords

UN SDGs

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