ABSTRACT
Introduction: Anti-angiogenetic agents are currently the most commonly used drugs for the treatment of colorectal cancer (CRC) patients, including various inhibitors targeting the epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and VEGF receptors (VEGFRs). Fruquintinib (HMPL-013), a highly selective and long-term small-molecule inhibitor of VEGFR (VEGFR1, 2, and 3) was recently approved in China for CRC treatment. Clinical studies have shown it has many advantages, such as low off-target toxicity, good drug tolerance, and strong effect.
Areas covered: In the review, the molecular structure, mechanism of action, pharmacokinetics, clinical efficacy, and safety of fruquintinib are introduced in detail. The potential clinic application on non-small cell lung cancer (NSCLC) and gastric cancer is also discussed.
Expert commentary: Fruquintinib was approved for patients with metastatic colorectal cancer (RAS wild type) who have previously received fluorouracil, oxaliplatin, and irinotecan-based chemotherapy and who have received or are not suitable for anti- VEGF therapy and anti- EGFR therapy. As a novel, therapeutic approach to CRC, Fruquintinib could be used as a third-line drug for the treatment of CRC patients. Due to drug resistance during the long-term therapy, the combination of fruquintinib with other targeted therapy drugs may be an effective option for CRC treatment.
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Article Highlights
Chemical name:
HMPL-013, chemical name is 6-(6,7-dimethoxyquinazolin-4-yloxy)-N,2-dimethyl benzofuran-3-carboxamide
Mechanism of action: a highly selective long-term inhibitor of VEGFR (VEGFR1,2, and 3)
Pharmacokinetics: Cmax is 2 h, bioavailability is about 100% with tissue distribution mainly in the gastrointestinal tract, liver, kidney, adrenal and adipose, T1/2 is 33.4 h.
Indication: CRC, NCSLC, gastric cancer
Route of administration: oral
Dose: 5 mg/day on a 3-week-on/1-week-off treatment cycle
Most frequent AEs: hypertension, skin reactions in the hands and feet, proteinuria, and diarrhea
Clinical trials (detail in ):
Phase 1: NCT01645215 (tumor), NCT02689752 (health), NCT01955304 (health), NCT03251378 (advanced solid tumor);
Phase 1 and 2: NCT01975077 (CRC), NCT02415023 (Gastric cancer);
Phase 2: NCT02196688 (CRC), NCT03684967 (lung cancer), NCT02976116 (NCSLC), NCT02590965 (NCSLC)
Phase 3: NCT02314819 (CRC), NCT02691299 (NCSLC), NCT03223376 (advanced gastric cancer)
Acknowledgments
Thanks, Dr. Kelly Ann Koral (Department of Pathology, School of Medicine, University of Pittsburgh) for her careful revision on the writing of the manuscript.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose. Hutchison China MediTech Limited provided a scientific accuracy review at the request of the journal editor.
Correction Statement
This article has been republished with minor changes. These changes do not impact the academic content of the article.