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Ref Type Journal Article
PMID (27975152)
Authors Van Laethem JL, Riess H, Jassem J, Haas M, Martens UM, Weekes C, Peeters M, Ross P, Bridgewater J, Melichar B, Cascinu S, Saramak P, Michl P, Van Brummelen D, Zaniboni A, Schmiegel W, Dueland S, Giurescu M, Garosi VL, Roth K, Schulz A, Seidel H, Rajagopalan P, Teufel M, Childs BH
Title Phase I/II Study of Refametinib (BAY 86-9766) in Combination with Gemcitabine in Advanced Pancreatic cancer.
Journal Targeted oncology
Vol 12
Issue 1
Date 2017 02
URL
Abstract Text 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/m2 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.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown pancreatic cancer not applicable Gemcitabine + Refametinib Phase Ib/II Actionable In a Phase I/II trial, Refametinib (BAY86-9766) and Gemzar (gemcitabine) combination treatment resulted in an objective response rate of 23% and a disease control rate of 73% in patients with advanced pancreatic cancer (PMID: 27975152). 27975152