| Title |
Phase I/II Study of Refametinib (BAY 86-9766) in Combination with Gemcitabine in Advanced Pancreatic cancer
|
|---|---|
| Published in |
Targeted Oncology, December 2016
|
| DOI | 10.1007/s11523-016-0469-y |
| Pubmed ID | |
| Authors |
Jean-Luc Van Laethem, Hanno Riess, Jacek Jassem, Michael Haas, Uwe M. Martens, Colin Weekes, Marc Peeters, Paul Ross, John Bridgewater, Bohuslav Melichar, Stefano Cascinu, Piotr Saramak, Patrick Michl, David Van Brummelen, Alberto Zaniboni, Wollf Schmiegel, Svein Dueland, Marius Giurescu, Vittorio L. Garosi, Katrin Roth, Anke Schulz, Henrik Seidel, Prabhu Rajagopalan, Michael Teufel, Barrett H. Childs |
| Abstract |
Activating KRAS mutations are reported in up to 90% of pancreatic cancers. Refametinib potently inhibits MEK1/2, part of the MAPK signaling pathway. This phase I/II study evaluated the safety and efficacy of refametinib plus gemcitabine in patients with advanced pancreatic cancer. Phase I comprised dose escalation, followed by phase II expansion. Refametinib and gemcitabine plasma levels were analyzed for pharmacokinetics. KRAS mutational status was determined from circulating tumor DNA. Ninety patients overall received treatment. The maximum tolerated dose was refametinib 50 mg twice daily plus standard gemcitabine (1000 mg/m(2) weekly). The combination was well tolerated, with no pharmacokinetic interaction. Treatment-emergent toxicities included thrombocytopenia, fatigue, anemia, and edema. The objective response rate was 23% and the disease control rate was 73%. Overall response rate, disease control rate, progression-free survival, and overall survival were higher in patients without detectable KRAS mutations (48% vs. 28%, 81% vs. 69%, 8.8 vs. 5.3 months, and 18.2 vs. 6.6 months, respectively). Refametinib plus gemcitabine was well tolerated, with a promising objective response rate, and had an acceptable safety profile and no pharmacokinetic interaction. There was a trend towards improved outcomes in patients without detectable KRAS mutations that deserves future investigation. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Japan | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 50% |
| Science communicators (journalists, bloggers, editors) | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 65 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 65 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 11 | 17% |
| Student > Ph. D. Student | 11 | 17% |
| Student > Master | 7 | 11% |
| Researcher | 6 | 9% |
| Student > Doctoral Student | 5 | 8% |
| Other | 10 | 15% |
| Unknown | 15 | 23% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 21 | 32% |
| Biochemistry, Genetics and Molecular Biology | 11 | 17% |
| Agricultural and Biological Sciences | 5 | 8% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 5% |
| Nursing and Health Professions | 2 | 3% |
| Other | 5 | 8% |
| Unknown | 18 | 28% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 December 2016.
All research outputs
#14,880,767
of 22,914,829 outputs
Outputs from Targeted Oncology
#242
of 551 outputs
Outputs of similar age
#241,908
of 420,768 outputs
Outputs of similar age from Targeted Oncology
#4
of 10 outputs
Altmetric has tracked 22,914,829 research outputs across all sources so far. This one is in the 32nd percentile – i.e., 32% of other outputs scored the same or lower than it.
So far Altmetric has tracked 551 research outputs from this source. They receive a mean Attention Score of 2.8. This one has gotten more attention than average, scoring higher than 52% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 420,768 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 39th percentile – i.e., 39% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 10 others from the same source and published within six weeks on either side of this one. This one has scored higher than 6 of them.