Randomized, Double-Blind, Phase II Study of Ruxolitinib or Placebo in Combination With Capecitabine in Patients With Metastatic Pancreatic Cancer for Whom Therapy With Gemcitabine Has Failed
Top Cited Papers
- 1 December 2015
- journal article
- research article
- Published by American Society of Clinical Oncology (ASCO) in Journal of Clinical Oncology
- Vol. 33 (34), 4039-4047
- https://doi.org/10.1200/jco.2015.61.4578
Abstract
Patients with advanced pancreatic adenocarcinoma have a poor prognosis and limited second-line treatment options. Evidence suggests a role for the Janus kinase (JAK)/signal transducer and activator of transcription pathway in the pathogenesis and clinical course of pancreatic cancer. In this double-blind, phase II study, patients with metastatic pancreatic cancer who had experienced treatment failure with gemcitabine were randomly assigned 1:1 to the JAK1/JAK2 inhibitor ruxolitinib (15 mg twice daily) plus capecitabine (1,000 mg/m2 twice daily) or placebo plus capecitabine. The primary end point was overall survival (OS); secondary end points included progression-free survival, clinical benefit response, objective response rate, and safety. Prespecified subgroup analyses evaluated treatment heterogeneity and efficacy in patients with evidence of inflammation. In the intent-to-treat population (ruxolitinib, n = 64; placebo, n = 63), the hazard ratio was 0.79 (95% CI, 0.53 to 1.18; P = .25) for OS and was 0.75 (95% CI, 0.52 to 1.10; P = .14) for progression-free survival. In a prespecified subgroup analysis of patients with inflammation, defined by serum C-reactive protein levels greater than the study population median (ie, 13 mg/L), OS was significantly greater with ruxolitinib than with placebo (hazard ratio, 0.47; 95% CI, 0.26 to 0.85; P = .011). Prolonged survival in this subgroup was supported by post hoc analyses of OS that categorized patients by the modified Glasgow Prognostic Score, a systemic inflammation–based prognostic system. Grade 3 or greater adverse events were observed with similar frequency in the ruxolitinib (74.6%) and placebo (81.7%) groups. Grade 3 or greater anemia was more frequent with ruxolitinib (15.3%; placebo, 1.7%). Ruxolitinib plus capecitabine was generally well tolerated and may improve survival in patients with metastatic pancreatic cancer and evidence of systemic inflammation.Keywords
This publication has 63 references indexed in Scilit:
- Cancer-related inflammation and treatment effectivenessThe Lancet Oncology, 2014
- The Role of Inflammation in Inflammatory Breast CancerAdvances in Experimental Medicine and Biology, 2014
- Prognostic and Predictive Blood-Based Biomarkers in Patients with Advanced Pancreatic Cancer: Results from CALGB80303 (Alliance)Clinical Cancer Research, 2013
- The systemic inflammation-based Glasgow Prognostic Score: A decade of experience in patients with cancerCancer Treatment Reviews, 2013
- JAK Inhibition with Ruxolitinib versus Best Available Therapy for MyelofibrosisNew England Journal of Medicine, 2012
- Janus kinase inhibitors for the treatment of myeloproliferative neoplasias and beyondNature Reviews Drug Discovery, 2011
- Safety and Efficacy of INCB018424, a JAK1 and JAK2 Inhibitor, in MyelofibrosisNew England Journal of Medicine, 2010
- TGF-β IL-6 axis mediates selective and adaptive mechanisms of resistance to molecular targeted therapy in lung cancerProceedings of the National Academy of Sciences, 2010
- IL-6 and Stat3 Are Required for Survival of Intestinal Epithelial Cells and Development of Colitis-Associated CancerCancer Cell, 2009
- Signal Transducer and Activator of Transcription 3 Is Required for the Oncogenic Effects of Non–Small-Cell Lung Cancer–Associated Mutations of the Epidermal Growth Factor ReceptorCancer Research, 2006