Ruxolitinib + capecitabine in advanced/metastatic pancreatic cancer after disease progression/intolerance to first-line therapy: JANUS 1 and 2 randomized phase III studies Journal Article
| Authors: | Hurwitz, H.; Van Cutsem, E.; Bendell, J.; Hidalgo, M.; Li, C. P.; Salvo, M. G.; Macarulla, T.; Sahai, V.; Sama, A.; Greeno, E.; Yu, K. H.; Verslype, C.; Dawkins, F.; Walker, C.; Clark, J.; O’Reilly, E. M. |
| Article 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/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. © 2018, Springer Science+Business Media, LLC, part of Springer Nature. |
| Keywords: | clinical trial; pancreatic neoplasms; jak1 protein tyrosine kinase; jak2 protein tyrosine kinase |
| Journal Title: | Investigational New Drugs |
| Volume: | 36 |
| Issue: | 4 |
| ISSN: | 0167-6997 |
| Publisher: | Springer |
| Date Published: | 2018-08-01 |
| Start Page: | 683 |
| End Page: | 695 |
| Language: | English |
| DOI: | 10.1007/s10637-018-0580-2 |
| PROVIDER: | scopus |
| PUBMED: | 29508247 |
| PMCID: | PMC6752723 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 4 September 2018 -- Source: Scopus |
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