A Phase-2 Trial of Single Agent Axitinib as Maintenance Therapy Following First-Line Treatment With Modified FOLFOX/Bevacizumab in Patients With Metastatic Colorectal Cancer

Bendell, Johanna C.; Joseph, Mathew J.; Barnes, Kirk; Mainwaring, Mark G.; Shipley, Dianna; Reddy, Chandra; Blakely, L. Johnetta; Blachly, Ronald; Lane, Cassie M.; Earwood, Chris; Kuzur, Michel E.

doi:10.1080/07357907.2017.1310221

Cited by 7 publications

(5 citation statements)

References 18 publications

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“…Compound 4 was evaluated in phase II trials for efficacy and safety as a first-line maintenance therapy for mCRC. In both trials, 4 demonstrated to be an effective agent in the first-line maintenance therapy of mCRC, a promising candidate for the maintenance therapy of mCRC [55,56]. A combination of 4 and navitoclax (ABT263, an antagonist of the Bcl-2 family with selective binding to the apoptosis suppressors Bcl-2 and Bcl-XL) has shown synergistic effects on RAmutant colon cancer cells.…”

Section: Nintedanib (1) (Methyl 2-hydroxy-3-[n-[4-[methyl-[2-(4-methy...mentioning

confidence: 99%

Emerging Therapeutic Agents for Colorectal Cancer

et al. 2021

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There are promising new therapeutic agents for CRC patients, including novel small-molecule inhibitors and immune checkpoint blockers. We focused on emerging CRC’s therapeutic agents that have shown the potential for progress in clinical practice. This review provides an overview of tyrosine kinase inhibitors targeting VEGF and KIT, BRAF and MEK inhibitors, TLR9 agonist, STAT3 inhibitors, and immune checkpoint blockers (PD1/PDL-1 inhibitors), for which recent advances have been reported. These new agents have the potential to provide benefits to CRC patients with unmet medical needs.

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Section: Nintedanib (1) (Methyl 2-hydroxy-3-[n-[4-[methyl-[2-(4-methy...mentioning

confidence: 99%

Emerging Therapeutic Agents for Colorectal Cancer

et al. 2021

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“…The initial oral dose of axitinib was 5 mg twice daily, and after 2 weeks of administration, the dose was increased to 7 mg twice daily in those patients that were able to tolerate axitinib well. As the primary endpoint, the median PFS was 8.3 months and the results showed that the efficacy of axitinib was comparable to that of other first-line maintenance drugs 60…”

Section: Clinical Trials In Mcrcmentioning

confidence: 92%

<p>Fruquintinib: a novel antivascular endothelial growth factor receptor tyrosine kinase inhibitor for the treatment of metastatic colorectal cancer</p>

Zhang

Zou

Wang

et al. 2019

CMAR

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Angiogenesis plays a critical role in the neoplastic growth, progression, and metastasis of colorectal cancer (CRC) in a process regulated by vascular endothelial growth factor (VEGF) family members and their receptors (VEGFR). Several small-molecule anti-VEGFR tyrosine kinase inhibitors (TKIs), such as regorafenib, famitinib, axitinib and apatinib, have been shown to be effective in treating metastatic colorectal cancer (mCRC). Fruquintinib (ELUNATE ® ) is a novel oral anti-VEGFR TKI, originated and developed by Hutchison MediPharma. Fruquintinib is a potent and highly selective small-molecule inhibitor of VEGFR-1, -2 and -3. In the Phase 3 FRESCO trial, fruquintinib improved both overall survival (OS) and progression-free survival (PFS) in patients with mCRC, compared with placebo. Fruquintinib also showed an acceptable safety and tolerability profile. Based on the data from this trial, fruquintinib was approved by the China Food and Drug Administration (CFDA) in 2018, for the treatment of patients with mCRC who had undergone at least two prior standard anticancer therapies. The existing clinical trials and future prospects of fruquintinib in mCRC will be discussed in this article. In addition, to better understand the role of fruquintinib in this setting, recent advances in other anti-VEGFR TKIs for mCRC treatment are also reviewed herein.

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“…Various TKIs other than regorafenib are under investigation for pretreated mCRC patients in order to improve the outcome in this setting, with some showing efficacy and an acceptable safety profile (Table 4) [74][75][76][77][78][79][80]. III, double-blind, placebo-controlled.…”

Section: Regorafenibmentioning

confidence: 99%

Molecular-Biology-Driven Treatment for Metastatic Colorectal Cancer

Lai

Liscia

Donisi

et al. 2020

Cancers

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Background: Metastatic CRC (mCRC) is a molecular heterogeneous disease. The aim of this review is to give an overview of molecular-driven treatment of mCRC patients. Methods: A review of clinical trials, retrospective studies and case reports was performed regarding molecular biomarkers with therapeutic implications. Results: RAS wild-type status was confirmed as being crucial for anti-epidermal growth factor receptor (EGFR) monoclonal antibodies and for rechallenge strategy. Antiangiogenic therapies improve survival in first- and second-line settings, irrespective of RAS status, while tyrosine kinase inhibitors (TKIs) remain promising in refractory mCRC. Promising results emerged from anti-HER2 drugs trials in HER2-positive mCRC. Target inhibitors were successful for BRAFV600E mutant mCRC patients, while immunotherapy was successful for microsatellite instability-high/defective mismatch repair (MSI-H/dMMR) or DNA polymerase epsilon catalytic subunit (POLE-1) mutant patients. Data are still lacking on NTRK, RET, MGMT, and TGF-β, which require further research. Conclusion: Several molecular biomarkers have been identified for the tailored treatment of mCRC patients and multiple efforts are currently ongoing to increase the therapeutic options. In the era of precision medicine, molecular-biology-driven treatment is the key to impro patient selection and patient outcomes. Further research and large phase III trials are required to ameliorate the therapeutic management of these patients.

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A Phase-2 Trial of Single Agent Axitinib as Maintenance Therapy Following First-Line Treatment With Modified FOLFOX/Bevacizumab in Patients With Metastatic Colorectal Cancer

Cited by 7 publications

References 18 publications

Emerging Therapeutic Agents for Colorectal Cancer

Emerging Therapeutic Agents for Colorectal Cancer

<p>Fruquintinib: a novel antivascular endothelial growth factor receptor tyrosine kinase inhibitor for the treatment of metastatic colorectal cancer</p>

Molecular-Biology-Driven Treatment for Metastatic Colorectal Cancer

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