PMID- 29750040
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220317
IS  - 1178-6930 (Print)
IS  - 1178-6930 (Electronic)
IS  - 1178-6930 (Linking)
VI  - 11
DP  - 2018
TI  - A Phase Ib study of ruxolitinib + gemcitabine +/- nab-paclitaxel in patients with 
      advanced solid tumors.
PG  - 2399-2407
LID - 10.2147/OTT.S157331 [doi]
AB  - 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). CONCLUSION: 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.
FAU - Bauer, Todd M
AU  - Bauer TM
AD  - Medical Oncology, Sarah Cannon Research Institute, Nashville, TN, USA.
AD  - Medical Oncology, Tennessee Oncology, Nashville, TN, USA.
FAU - Patel, Manish R
AU  - Patel MR
AD  - Medical Oncology, Sarah Cannon Research Institute, Nashville, TN, USA.
AD  - Medical Oncology, Florida Cancer Specialists, Sarasota, FL, USA.
FAU - Forero-Torres, Andres
AU  - Forero-Torres A
AD  - Hematology and Oncology Division, University of Alabama at Birmingham, 
      Birmingham, AL, USA.
FAU - George, Thomas J Jr
AU  - George TJ Jr
AD  - Department of Medicine, University of Florida, Gainesville, FL, USA.
FAU - Assad, Albert
AU  - Assad A
AD  - Biostatistics, Incyte Corporation, Wilmington, DE, USA.
FAU - Du, Yining
AU  - Du Y
AD  - Biostatistics, Incyte Corporation, Wilmington, DE, USA.
FAU - Hurwitz, Herbert
AU  - Hurwitz H
AD  - Department of Medicine, Duke University Medical Center, Durham, NC, USA.
LA  - eng
PT  - Journal Article
DEP - 20180430
PL  - New Zealand
TA  - Onco Targets Ther
JT  - OncoTargets and therapy
JID - 101514322
PMC - PMC5935192
OTO - NOTNLM
OT  - Janus kinase inhibitor
OT  - pancreatic cancer
COIS- Disclosure Both AA and YD are employees of Incyte Corporation and have stock 
      ownership. The authors report no other conflicts of interest in this work.
EDAT- 2018/05/12 06:00
MHDA- 2018/05/12 06:01
PMCR- 2018/04/30
CRDT- 2018/05/12 06:00
PHST- 2018/05/12 06:00 [entrez]
PHST- 2018/05/12 06:00 [pubmed]
PHST- 2018/05/12 06:01 [medline]
PHST- 2018/04/30 00:00 [pmc-release]
AID - ott-11-2399 [pii]
AID - 10.2147/OTT.S157331 [doi]
PST - epublish
SO  - Onco Targets Ther. 2018 Apr 30;11:2399-2407. doi: 10.2147/OTT.S157331. 
      eCollection 2018.