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A Phase Ib study of ruxolitinib + gemcitabine ± nab-paclitaxel in patients with advanced solid tumors

Authors Bauer TM, Patel MR, Forero-Torres A, George TJ Jr, Assad A, Du Y, Hurwitz H

Received 21 November 2017

Accepted for publication 17 March 2018

Published 30 April 2018 Volume 2018:11 Pages 2399—2407


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Faris Farassati

Todd M Bauer,1,2 Manish R Patel,1,3 Andres Forero-Torres,4 Thomas J George Jr,5 Albert Assad,6 Yining Du,6 Herbert Hurwitz7

1Medical Oncology, Sarah Cannon Research Institute, Nashville, TN, USA; 2Medical Oncology, Tennessee Oncology, Nashville, TN, USA; 3Medical Oncology, Florida Cancer Specialists, Sarasota, FL, USA; 4Hematology and Oncology Division, University of Alabama at Birmingham, Birmingham, AL, USA; 5Department of Medicine, University of Florida, Gainesville, FL, USA; 6Biostatistics, Incyte Corporation, Wilmington, DE, USA; 7Department of Medicine, Duke University Medical Center, Durham, NC, USA

Purpose: Aberrant activation of the Janus-associated kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is associated with increased malignant cell proliferation and survival. This Phase Ib study evaluated ruxolitinib, a potent JAK1/2 inhibitor, in combination with gemcitabine with or without nab-paclitaxel in patients with advanced solid tumors.
Patients and methods: Patients received ruxolitinib + gemcitabine (regimen A) or ruxolitinib + gemcitabine + nab-paclitaxel (regimen B). The objective of the dose-finding phase was to identify the maximum tolerated doses (MTDs) of ruxolitinib plus gemcitabine with or without nab-paclitaxel.
Results: Among 42 patients enrolled, the median age was 62.5 years, 81.0% had pancreatic cancer, and almost 62% had received prior systemic therapy. Regimen A was tolerated with standard doses of gemcitabine; regimen B was tolerated with reduced doses of gemcitabine/nab-paclitaxel or concomitant granulocyte colony-stimulating factor. The sponsor decided to terminate the study early due to the interim analysis results of the Phase III JANUS 1 study. Discontinuations were mainly due to radiologic or clinical disease progression (81.0% of patients). Median treatment durations were 55.5 days (cohort A0) and 150.5 days (pooled B cohorts). Four patients (pooled B cohorts) had dose-limiting toxicities: grade 3 pneumonia (n=1), grade 4 neutropenia (n=1), and grade 4 thrombocytopenia (n=2). The most common grade 3/4 hematologic adverse events (AEs) were anemia, thrombocytopenia, and neutropenia. Serious AEs occurring in ≥2 patients in cohort A0 or pooled B cohorts were abdominal pain, sepsis (cohort A0), dehydration, anemia, and asthenia (pooled B cohorts). Overall response rates (ORRs) were 12.5% in cohort A0 and 38.5% in pooled B cohorts. Among patients with pancreatic cancer, ORR was 23.5% (14.0% cohort A0 30.0% pooled B cohorts).
The study was terminated early prior to reaching MTDs per sponsor decision; although ruxolitinib plus gemcitabine with or without nab-paclitaxel was generally safe and well tolerated in patients with advanced solid tumors, this combination will not be pursued further.

Keywords: Janus kinase inhibitor, pancreatic cancer

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